The reading about mechanisms of resistance of to Taxol calls for a new strategy for treatment of triple negative breast cancer; while it is true that PARP inhibitor should still be considered in BRCA positive cancers, adding AURORA inhibitors seems to offer logically the best opportunity to increase the activity of proposed first line drugs.
Indeed, triple negative breast cancer assumes that the receptors to conventional stimulants of the breast cancer cell are not functional or responsive. Therefore, increasing the role of a direct attack of either the nuclear material or the microfilament/microtubule. Taxol - Cisplatin combination achieves that! Adding Avastin and other receptor stimulators could be a riskier proposition if you assume a questionable sensitivity of receptor in general. Your best bet is an action on the Histones and further DNA destruction. The cell division is your focus here and this is re-emphasized by the importance of CDKs as described by MD Anderson researchers. As a matter of fact, the AURORA inhibitors by binding to Adenine and to the Histone appear to offer a potential and logical choice to recruit in first line to boost response rates! So, pending proof of concept, we support the idea of adding Aurora inhibitors to a Taxane-Cisplatin core combination. Some of the Aurora Kinase also target CDKs and JAK2. These will be my choice for new trials!
After the cancer has seen chemotherapy, endothelial cells have been altered, hypoxia has been triggered by closure of some of the blood vessel closure, the MTOR has been stimulated, we believe adding the MTOR makes more sense. This has been also suggested after failure of Avastin, These concepts have been publicized, It is time to move to clinical trial! (FOR THOSE WHO CAN, WE HAVE OUR HANDS TIED BY HUMAN HISTORY!)
Showing posts with label avastin. Show all posts
Showing posts with label avastin. Show all posts
Tuesday, April 30, 2013
Friday, April 26, 2013
CONSIDERATIONS IN RECURRENT OVARIAN CANCER TREATMENT:
Nice discussion by
By Edward Tanner, MD1, Deborah K. Armstrong, MD2 | April 15, 2013
In summary, and I hope I dig this right!
That one thing you look at in recurrent Ovarian cancer:
ASSUMING YOUR FIRST TREATMENT WAS PLATINUM BASED, WHICH IS MOST OF THE TIME THE CASE, the disease free interval of more than 6 months (not 12 months) determines whether the disease is platinum sensitive. Because re-treatment should include platinum in those with the disease still sensitive!
The other sensitive notion was the issue of Cytoreduction, according to these authors, Cytoreduction in recurrent disease makes sens only if the Progression free interval was more than 1 year (here "12 months" is needed), and when the lesions could be realistically resected! ("gross resection is achievable")
The discussion on Target therapy was limited to:
1. Adding Avastin to Gemzar +platinum which has shown to increase progression free survival
2. to using PARP inhibitors for those with BRCA Mutation
---------------------------------------------------------------
In other news!
"Similarities Between Ovarian and Basal-Like Breast Cancers:
In a copy number and genomic mutation analysis of all four breast cancer subtypes and ovarian cancer tumor samples, basal-like breast cancer and ovarian cancer were found to be most similar. The authors highlight that the similarities between basal-like breast cancer and serous ovarian cancers indicate that these two difficult-to-treat cancer types may be able to be treated with the same therapies—chemotherapy drugs, anti-angiogenesis agents, and others in development."
No comment was reported about the difference on MUCIN genes!
" For both ovarian and basal-like breast cancer, TP53 was found mutated in 80% of tumors," pointing to the Receptor failure theory developed here!
"Basal-like breast cancers and ovarian cancers had similar rates of mutation and a similar spectrum of mutations. The basal-like tumors had a high frequency of mutations in the ATM, BRCA1, BRCA2, as well as RB1 loss and cyclin E1 amplification—the same mutations identified for ovarian cancers.
About 20% of basal-like breast tumors had a germline or somatic mutation in either BRCA1 or BRCA2. The authors suggest that these BRCA-mutated patients could potentially respond to Poly (ADP-ribose) polymerase (PARP) inhibitors. The analysis also showed various copy number amplifications and deletions that may be therapeutic targets."
For more, go to:
By Anna Azvolinsky, PhD1
----------------------------------------------------------------------------------------------------------------------
AND ALSO READ THIS:
By Edward Tanner, MD1, Deborah K. Armstrong, MD2 | April 15, 2013
In summary, and I hope I dig this right!
That one thing you look at in recurrent Ovarian cancer:
ASSUMING YOUR FIRST TREATMENT WAS PLATINUM BASED, WHICH IS MOST OF THE TIME THE CASE, the disease free interval of more than 6 months (not 12 months) determines whether the disease is platinum sensitive. Because re-treatment should include platinum in those with the disease still sensitive!
The other sensitive notion was the issue of Cytoreduction, according to these authors, Cytoreduction in recurrent disease makes sens only if the Progression free interval was more than 1 year (here "12 months" is needed), and when the lesions could be realistically resected! ("gross resection is achievable")
The discussion on Target therapy was limited to:
1. Adding Avastin to Gemzar +platinum which has shown to increase progression free survival
2. to using PARP inhibitors for those with BRCA Mutation
---------------------------------------------------------------
In other news!
"Similarities Between Ovarian and Basal-Like Breast Cancers:
In a copy number and genomic mutation analysis of all four breast cancer subtypes and ovarian cancer tumor samples, basal-like breast cancer and ovarian cancer were found to be most similar. The authors highlight that the similarities between basal-like breast cancer and serous ovarian cancers indicate that these two difficult-to-treat cancer types may be able to be treated with the same therapies—chemotherapy drugs, anti-angiogenesis agents, and others in development."
No comment was reported about the difference on MUCIN genes!
" For both ovarian and basal-like breast cancer, TP53 was found mutated in 80% of tumors," pointing to the Receptor failure theory developed here!
"Basal-like breast cancers and ovarian cancers had similar rates of mutation and a similar spectrum of mutations. The basal-like tumors had a high frequency of mutations in the ATM, BRCA1, BRCA2, as well as RB1 loss and cyclin E1 amplification—the same mutations identified for ovarian cancers.
About 20% of basal-like breast tumors had a germline or somatic mutation in either BRCA1 or BRCA2. The authors suggest that these BRCA-mutated patients could potentially respond to Poly (ADP-ribose) polymerase (PARP) inhibitors. The analysis also showed various copy number amplifications and deletions that may be therapeutic targets."
For more, go to:
Study Finds Ovarian and Basal-Like/Triple-Negative Breast Cancers Genetically Similar
----------------------------------------------------------------------------------------------------------------------
AND ALSO READ THIS:
ONCOLOGY.
Vol. 27
No. 1
mTOR Inhibitors in the Treatment of Breast Cancer
By Shaveta Vinayak, MD, MS1,
Robert W. Carlson, MD1 |
January 15, 2013
1Department of Medicine, Stanford University School of Medicine, Stanford, California
ABSTRACT: The phosphatidylinositol 3-kinase/mammalian target
of rapamycin (PI3K/mTOR) pathway is commonly dysregulated in breast
cancer. In preclinical studies, hyperactivation of the PI3K pathway has
been linked to resistance to both endocrine therapy and trastuzumab(Drug information on trastuzumab)
(Herceptin). Rapalogs, agents that primarily inhibit mTOR-raptor
complex 1, have been studied in combination with endocrine therapy to
overcome endocrine resistance. Trials of combination endocrine therapy
and rapalogs in metastatic hormone receptor–positive breast cancer have
demonstrated variable results. However, two independent trials have
recently shown that combination everolimus (Afinitor) and tamoxifen(Drug information on tamoxifen) or combination everolimus and exemestane(Drug information on exemestane)
(Aromasin) is more effective than either endocrine agent alone. These
trials selected patients with cancer refractory to endocrine therapy,
which may be important in sensitizing tumors to inhibition of this
pathway. In human epidermal growth factor receptor 2 (HER2)-positive
breast cancer, the early clinical data with combinations of PI3K/mTOR
inhibitors and anti-HER2 therapies are encouraging.
| |
Monday, March 11, 2013
AVASTIN and Blood Vessels
1. Avastin normalizes blood vessel and therefore improves drug delivery
2.Combination with anti-EGFR, shortens PFS
3. Changes endothelium
4. Refractoriness soon develops
5.no cures
6.lack of biomarkers to optimally evaluate,monitor efficacy, and therefore dose optimally
7.Increasing Fibroblast growth factor as a way of dealing with lack of VEGF receptors
?dummy receptor to hijack extracellular - transcription factors increase
INHIBITION OF MTOR
from R T Kurmasheva, et al
"Thus, inhibition of mTOR may have direct effects on cancer cell proliferation and survival, indirect effects via inhibition of HIF-1α, thus reducing tumour-elicited VEGF, direct effects on vascular endothelial cells, or vascular smooth muscle cells (Humar et al, 2002; Majumder et al, 2004). For example, induction of HIF-1α and VEGF by the CML-associated oncogene, BCR-ABL, is mTOR-dependent (Mayerhofer et al, 2002), and in vitro, rapamycin inhibited VEGF production in primary cultures from BCR-ABL transformed, imatinib resistant, CML (Mayerhofer et al, 2005). The role for mTOR in VEGF production is supported by regulation of HIF-1α by mTOR signalling and increased VEGF in cells deficient in the TSC that negatively regulates mTOR via Rheb (Hudson et al, 2002). However, other studies support a role mainly for PI3K and to a lesser extent mTOR being required for insulin-induced HIF-1α expression (Treins et al, 2002). Our studies indicate that rapamycin treatment has little effect on hypoxia-driven VEGF production in most rhabdomyosarcoma or neuroblastoma cell lines (Kurmasheva et al, submitted). Thus, in these cells it is unlikely that rapamycin would block tumour-derived VEGF, although it may directly block the response of vascular endothelial or other stromal cells in tumour tissue. Potentially, in vivo resistance to mTOR inhibition could be elicited by secretion of angiogenic factors that signal to stromal cells via mTOR-independent pathways to increase proliferation or motility of vascular cells."
------------------------------------------------------------------------------
Yesterday we saw that Anti-VEGF drug induced alteration of vascular endothelium that could eventually bring Hypoxia into the cell, today we add evidence that the Hypoxia may induce HIF expression bringing MTOR overexpression into the battle leading to cancer cellular survival. THIS INDICATES THAT WHILE CONTINUING AVASTIN, INTRODUCING MTOR INHIBITOR AT THIS POINT MAY BRING A NEW STRATEGY TO REVERSE AVASTIN RESISTANCE, MEANING WHEN PLACENTAL GROWTH FACTOR OVER EXPRESSION IS HIGH (A MARKER OF AVASTIN FAILURE) , IT WOULD BE AN APPROPRIATE TIME TO BRING IN THE MTOR WITHOUT STOPPING AVASTIN. REMEMBER STOPPING AVASTIN HAS DEVASTATING REBOUND OF CANCER. AVASTIN HERE SERVES AS A PRIME FOR MTOR!
"Thus, inhibition of mTOR may have direct effects on cancer cell proliferation and survival, indirect effects via inhibition of HIF-1α, thus reducing tumour-elicited VEGF, direct effects on vascular endothelial cells, or vascular smooth muscle cells (Humar et al, 2002; Majumder et al, 2004). For example, induction of HIF-1α and VEGF by the CML-associated oncogene, BCR-ABL, is mTOR-dependent (Mayerhofer et al, 2002), and in vitro, rapamycin inhibited VEGF production in primary cultures from BCR-ABL transformed, imatinib resistant, CML (Mayerhofer et al, 2005). The role for mTOR in VEGF production is supported by regulation of HIF-1α by mTOR signalling and increased VEGF in cells deficient in the TSC that negatively regulates mTOR via Rheb (Hudson et al, 2002). However, other studies support a role mainly for PI3K and to a lesser extent mTOR being required for insulin-induced HIF-1α expression (Treins et al, 2002). Our studies indicate that rapamycin treatment has little effect on hypoxia-driven VEGF production in most rhabdomyosarcoma or neuroblastoma cell lines (Kurmasheva et al, submitted). Thus, in these cells it is unlikely that rapamycin would block tumour-derived VEGF, although it may directly block the response of vascular endothelial or other stromal cells in tumour tissue. Potentially, in vivo resistance to mTOR inhibition could be elicited by secretion of angiogenic factors that signal to stromal cells via mTOR-independent pathways to increase proliferation or motility of vascular cells."
------------------------------------------------------------------------------
Yesterday we saw that Anti-VEGF drug induced alteration of vascular endothelium that could eventually bring Hypoxia into the cell, today we add evidence that the Hypoxia may induce HIF expression bringing MTOR overexpression into the battle leading to cancer cellular survival. THIS INDICATES THAT WHILE CONTINUING AVASTIN, INTRODUCING MTOR INHIBITOR AT THIS POINT MAY BRING A NEW STRATEGY TO REVERSE AVASTIN RESISTANCE, MEANING WHEN PLACENTAL GROWTH FACTOR OVER EXPRESSION IS HIGH (A MARKER OF AVASTIN FAILURE) , IT WOULD BE AN APPROPRIATE TIME TO BRING IN THE MTOR WITHOUT STOPPING AVASTIN. REMEMBER STOPPING AVASTIN HAS DEVASTATING REBOUND OF CANCER. AVASTIN HERE SERVES AS A PRIME FOR MTOR!
THE CRCBM RECOMMENDS THIS PIECE OF ARTICLE TO ALL READERS!
Mechanisms of Resistance to Anti-Angiogenic Therapy and Development of Third-Generation Anti-Angiogenic Drug Candidates
+ Author Affiliations
- P. Carmeliet, MD, PhD, Vesalius Research Center, VIB, K.U. Leuven, Campus Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium Email: peter.carmeliet@med.kuleuven.be
- -----------------------------------------------------------------------------------------
- Suffice is to say that the concerns mentioned in this review, which is an excellent review, unveils in pretty good details the insufficiency of a monotherapy attacking an essential function of the cells. Not only will the cell have an answer such as dummy receptors, secondary amplification of transcription factors of growth factors, but escape mechanisms that include escape of the area leading to metastasis. I should confess that recruiting other cells to help fight the attacker (Myeloid and endothelial cells) showed clearly how much angiogenesis is globally needed. I would think that the reaction by the NF-kB would be sufficient; with its secondary growth factor production, induction would be the predictable way. But clearly, the cell wants restoration of the angiogenic function and finally wins, making Avastin effects short lived. By inducing Hypoxia, stress becomes a secondary impetus and c-JUN enters the dance and fights again with resulting amplification of growth factor and various dislocation of various cyclins at integrin locations including the Angiopoietins.
- One of the things that needs to be emphasized or not looked at or discussed in your piece are events happening at the MEK. You know by now that MEK is clearly amplified either by the cancerous process or in reaction to the blockage or consumption at VEGF. Tracking MEK is important, because if amplified and mutated it may reverse mesengial transformation and render the cell more omnipotent. It may be at the center of the observation that blocking both EGFR and VEGF reduces the progression free survival. Events at the MEK need to be scrutinized.
- You also realize that, in the long run, MTOR will be secondarily stimulated leading to Telomere preservation (stabilization) and cell surviva
- The quick restoration of the angiogenic function after cessation of the treatment marks the importance of VEGF.
Clearly, Avastin is never meant to be a monotherapy, that is the answer! To all action, there is a reaction. And cells expect action, it is built for them!
Sunday, March 10, 2013
METASTATIC COLON CANCER
*It is interesting to note that in current clinical practice 3/4 of Oncologist still give Avastin instead of Cetuximab as their first choice in KRAS wild type metastatic colon cancer, and they chose it in combination with FOLFOX. Why to do the test at onset. And 12 cycles won rather than "until disease progression" in Metastatic setting.
* If you worry about Mismatch repair, it did not come up!
*Avastin-Xeloda superior to Xeloda alone with
- progression free survival (PFS) 9.1 months Vs 6.1months
- Overall survival (OS) 20.7 months Vs 16.8 months
* In Maintenance setting, Combining Avastin to Erlotinib was superior to Avastin alone (OPTIMOX3) in terms of progression free survival.
*In the VELOUR study
Aflibercept +FOLFIRI was superior to Folfiri alone in terms of PFS and OS.
*new kid on the block Regorafenib (brings back use of EUCERIN cream for patients palms)
* If you worry about Mismatch repair, it did not come up!
*Avastin-Xeloda superior to Xeloda alone with
- progression free survival (PFS) 9.1 months Vs 6.1months
- Overall survival (OS) 20.7 months Vs 16.8 months
* In Maintenance setting, Combining Avastin to Erlotinib was superior to Avastin alone (OPTIMOX3) in terms of progression free survival.
*In the VELOUR study
Aflibercept +FOLFIRI was superior to Folfiri alone in terms of PFS and OS.
*new kid on the block Regorafenib (brings back use of EUCERIN cream for patients palms)
Saturday, March 9, 2013
RECURRENT LIPOSARCOMA
The other day we were in a conference discussing a case of Liposarcoma. The man was in his 50ies and had been referred to the University surgeon for an extensive abdominal Liposarcoma that needed further resection. The disease had been resected at least twice by the community surgeon before, it had returned with significant peritoneal and pelvic infiltration. Interval between resections had been in years, but now it was in months. Clearly, the disease has packed further gene abnormalities now that it is evidently metastatic. Let me take this back, because despite the widespread invasion in the abdomen, there was no tissue invasion. There were no clear liver, lung or brain invasion. This disease was killing a man before our eyes because of clear infiltration of abdominal tissues.
Because of the interval between surgeries, the Oncologist argued that this is a low grade tumor and may not be handled with standard chemotherapy and I strongly believe he was right. My case with Angiosarcoma did not budge with Gemzar, Taxol followed by MAID, I am trying AVASTIN ALONE now!
But returning to the case, the hospital and the surgery department are now breathing on the neck of the surgeon because they do not see the point of putting the patient through very expensive surgeries followed by costly ICU stays every few months. I guess there are potential liabilities linked to the exercise. Particularly because the surgeries were done when this patient was with evident big progression of disease, but asymptomatic still. Oncologist and Surgeon alike argued we should not wait for symptoms, because it could be inoperable by then, and an aggressive surgery plan is helpful in these local diseases.
With standard chemotherapy out the only thing left is Target therapy as an effective option. We did not get help from the pathology department since no genetic abnormality testing is done (this is not Mayo or Harvard. DR KRIS who speaks of gene panels in lung cancer does not live here). And Votrient, the only FDA approved drug is indicated in those who failed chemotherapy. Basically, you have to put this man on chemotherapy that you know will harm him unnecessarily in order to get to Votrient (Pazopanib), an anti-VEGFR(s), Anti-c-KIT, anti-PDGFR a/Beta. with 3-4 months advantage over placebo.
-------------------------------------------------------------------------------------------
Media Inquiries: Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA approves Votrient for advanced soft tissue sarcoma
The U.S. Food and Drug Administration today approved Votrient (pazopanib) to treat patients with advanced soft tissue sarcoma who have previously received chemotherapy. Soft tissue sarcoma is a cancer that begins in the muscle, fat, fibrous tissue, and other tissues.
Votrient is a pill that works by interfering with angiogenesis, the growth of new blood vessels needed for solid tumors to grow and survive.
A rare cancer with many subtypes, soft tissue sarcoma occurs in about 10,000 cases annually in the United States. More than 20 subtypes of sarcoma were included in the clinical trial leading to approval of Votrient. The drug is not approved for patients with adipocytic soft tissue sarcoma and gastrointestinal stromal tumors.
“Soft tissue sarcomas are a diverse group of tumors and the approval of Votrient for this general class of tumors is the first in decades,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Drug development for sarcomas has been especially challenging because of the limited number of patients and multiple subtypes of sarcomas.”
The safety and effectiveness of Votrient was evaluated in a single clinical study in 369 patients with advanced soft tissue sarcoma who had received prior chemotherapy. Patients were randomly selected to receive Votrient or a placebo. The study was designed to measure the length of time a patient lived without the cancer progressing (progression-free survival). The disease did not progress for a median of 4.6 months for patients receiving Votrient, compared with 1.6 months for those receiving the placebo.
The most common side effects in Votrient-treated patients were fatigue, diarrhea, nausea, weight loss, high blood pressure, decreased appetite, vomiting, tumor and muscle pain, hair color changes, headache, a distorted sense of taste, shortness of breath, and skin discoloration.
Votrient carries a boxed warning alerting patients and health care professionals to the potential risk of liver damage (hepatotoxicity), which can be fatal. Patients should be monitored for liver function and treatment should be discontinued if liver function declines.
Votrient was granted an orphan drug status designation for this indication. An orphan designation is given to a drug intended to treat a disease affecting fewer than 200,000 patients in the United States. Votrient was first approved in October 2009 for the treatment of advanced kidney cancer.
Votrient is marketed by GlaxoSmithKline of Research Triangle Park, N.C.
For more information:
FDA: Office of Hematology and Oncology Products
FDA: Approved Drugs: Questions and Answers
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Because of the interval between surgeries, the Oncologist argued that this is a low grade tumor and may not be handled with standard chemotherapy and I strongly believe he was right. My case with Angiosarcoma did not budge with Gemzar, Taxol followed by MAID, I am trying AVASTIN ALONE now!
But returning to the case, the hospital and the surgery department are now breathing on the neck of the surgeon because they do not see the point of putting the patient through very expensive surgeries followed by costly ICU stays every few months. I guess there are potential liabilities linked to the exercise. Particularly because the surgeries were done when this patient was with evident big progression of disease, but asymptomatic still. Oncologist and Surgeon alike argued we should not wait for symptoms, because it could be inoperable by then, and an aggressive surgery plan is helpful in these local diseases.
With standard chemotherapy out the only thing left is Target therapy as an effective option. We did not get help from the pathology department since no genetic abnormality testing is done (this is not Mayo or Harvard. DR KRIS who speaks of gene panels in lung cancer does not live here). And Votrient, the only FDA approved drug is indicated in those who failed chemotherapy. Basically, you have to put this man on chemotherapy that you know will harm him unnecessarily in order to get to Votrient (Pazopanib), an anti-VEGFR(s), Anti-c-KIT, anti-PDGFR a/Beta. with 3-4 months advantage over placebo.
-------------------------------------------------------------------------------------------
FDA NEWS RELEASE
For Immediate Release: April 26, 2012Media Inquiries: Erica Jefferson, 301-796-4988, erica.jefferson@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA approves Votrient for advanced soft tissue sarcoma
The U.S. Food and Drug Administration today approved Votrient (pazopanib) to treat patients with advanced soft tissue sarcoma who have previously received chemotherapy. Soft tissue sarcoma is a cancer that begins in the muscle, fat, fibrous tissue, and other tissues.
Votrient is a pill that works by interfering with angiogenesis, the growth of new blood vessels needed for solid tumors to grow and survive.
A rare cancer with many subtypes, soft tissue sarcoma occurs in about 10,000 cases annually in the United States. More than 20 subtypes of sarcoma were included in the clinical trial leading to approval of Votrient. The drug is not approved for patients with adipocytic soft tissue sarcoma and gastrointestinal stromal tumors.
“Soft tissue sarcomas are a diverse group of tumors and the approval of Votrient for this general class of tumors is the first in decades,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Drug development for sarcomas has been especially challenging because of the limited number of patients and multiple subtypes of sarcomas.”
The safety and effectiveness of Votrient was evaluated in a single clinical study in 369 patients with advanced soft tissue sarcoma who had received prior chemotherapy. Patients were randomly selected to receive Votrient or a placebo. The study was designed to measure the length of time a patient lived without the cancer progressing (progression-free survival). The disease did not progress for a median of 4.6 months for patients receiving Votrient, compared with 1.6 months for those receiving the placebo.
The most common side effects in Votrient-treated patients were fatigue, diarrhea, nausea, weight loss, high blood pressure, decreased appetite, vomiting, tumor and muscle pain, hair color changes, headache, a distorted sense of taste, shortness of breath, and skin discoloration.
Votrient carries a boxed warning alerting patients and health care professionals to the potential risk of liver damage (hepatotoxicity), which can be fatal. Patients should be monitored for liver function and treatment should be discontinued if liver function declines.
Votrient was granted an orphan drug status designation for this indication. An orphan designation is given to a drug intended to treat a disease affecting fewer than 200,000 patients in the United States. Votrient was first approved in October 2009 for the treatment of advanced kidney cancer.
Votrient is marketed by GlaxoSmithKline of Research Triangle Park, N.C.
For more information:
FDA: Office of Hematology and Oncology Products
FDA: Approved Drugs: Questions and Answers
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
#
,
-------------------------------------------------------------------------------------
For the sake of argument
1. In this man we know it is a Liposarcoma
therefore the primary deficiency is in the handling of lipid. Insulin Receptor, may be? IGFR, IGFBP, PPR1. CCR11
(GOT TO RUN TO CONFERENCE WITH XCENDA IN CHICAGO---TO BE CONTINUED!)
(GOT TO RUN TO CONFERENCE WITH XCENDA IN CHICAGO---TO BE CONTINUED!)
-
Wednesday, February 27, 2013
PREVENTABLE CANCER DEATH, AND YOU CAN'T DO A THING! AND THIS IS TEXAS/ USA!
HOW DO YOU LOOK AT A MAN 2 YEARS BEFORE HIS PREVENTABLE CANCER DEATH, AND YOU CAN'T DO A THING! AND THIS IS TEXAS/ USA!
Just got off the phone with a wife of a man with stage IIIB Penile cancer. Their largest problem is not the cancer, but the lack of insurance and lack of money. He needs Cisplatin, a drug older than myself, but can't afford it. He has positive inguinal node but can't afford a consultation with the radiation therapy DR. What to do? As an Oncologist I am offering my service, but this is not going to save the man.
It is a time like this that challenges your soul, you just want to run from this misery of mind and hide!
It is a time like this that universal Insurance makes complete sense, but it will come too late for this one man!
If you can help, call our clinic 915-307- 3354! And it is not the only case, I also have this 38 year old woman with unresectable Angiosarcomas in the liver.... same story....call if you can help!
Just got off the phone with a wife of a man with stage IIIB Penile cancer. Their largest problem is not the cancer, but the lack of insurance and lack of money. He needs Cisplatin, a drug older than myself, but can't afford it. He has positive inguinal node but can't afford a consultation with the radiation therapy DR. What to do? As an Oncologist I am offering my service, but this is not going to save the man.
It is a time like this that challenges your soul, you just want to run from this misery of mind and hide!
It is a time like this that universal Insurance makes complete sense, but it will come too late for this one man!
If you can help, call our clinic 915-307- 3354! And it is not the only case, I also have this 38 year old woman with unresectable Angiosarcomas in the liver.... same story....call if you can help!
Friday, February 22, 2013
ANTI-MEK ARE BETTER ANTI-VEGF
Based on what we know now, it is easy to see that in those diseases where Avastin has failed FDA approval, Anti-MEK will do better. MEK is down stream and MEK is involved in much more, including VEGF expression. MEK is part of the MEK/MAPK pathways, it is the door to Mesenchymal transformation (that is it the door to epithelial-mesenchymal transition), and therefore to angiogenesis, and to metastatic spread.
Anti-MEK also removes the negative inhibitory effect of the PTEN driven forces of the PI3K/MTOR pathways.
Metastatic Colon Cancer is the Primary target!
Only the MTOR inhibitors add to these drugs
Inability of Doxorubicin to add to DTIC in Melanoma is due to amplification of these 2 pathways.
Anti-MEK and MTOR combination will do far better in Melanoma and Pancreatic cancers, mark my words. We just need to brace ourselves to a new set of side effects.
Based on what we know now, it is easy to see that in those diseases where Avastin has failed FDA approval, Anti-MEK will do better. MEK is down stream and MEK is involved in much more, including VEGF expression. MEK is part of the MEK/MAPK pathways, it is the door to Mesenchymal transformation (that is it the door to epithelial-mesenchymal transition), and therefore to angiogenesis, and to metastatic spread.
Anti-MEK also removes the negative inhibitory effect of the PTEN driven forces of the PI3K/MTOR pathways.
PTEN inhibits insulin-stimulated MEK/MAPK activation andcell growth by blocking IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex formation in a breast cancer model
- (Liang-Ping Weng1 at al.) The involvement of the Sons of the Sevenless could signify a large implication on the RAS pathway. And Anti-MEK were used as Medication to be used in lung cancer displaying amplification of the K-RAS
Metastatic Colon Cancer is the Primary target!
Only the MTOR inhibitors add to these drugs
Inability of Doxorubicin to add to DTIC in Melanoma is due to amplification of these 2 pathways.
Anti-MEK and MTOR combination will do far better in Melanoma and Pancreatic cancers, mark my words. We just need to brace ourselves to a new set of side effects.
Tuesday, February 12, 2013
PLATELET DERIVED GROWTH FACTOR, A DEADLY MISNOMER
====================================================
By naming this compound PDGF, the scientist who described this cytokine not only picked the wrong name,
but also sent researchers on the wrong path to understanding just how important this growth factor is. As a result, some people are probably dying because the emphasis brought by the name was not clearly defined.
First of all, PDGF does not come solely from Platelets alone. It is made by a number of cells including Muscle cells, Endothelial cells and even Macrophages.
And when you think of Platelets, Coagulation comes to mind, weakening of platelets and the like. If this PDGF does this, it is at a strictly minimal or insignificant level. The effect on Platelets is only mentioned by those who clearly have been fooled and kept looking for rare effects which eventually can be found. This PDGF works on Mesenchymal cells since creation. It participates in Embryogenesis, cell survival, proliferation, angiogenesis and differentiation. In adults, its main effect is on Fibroblast and Glial cells.
When you think Platelet, platelet Aggregation, adhesion and so forth. PDGF kills by Fibrosis in cirrhosis of the liver and Pulmonary hypertension, one of the worse silent killers of our time. Pulmonary Hypertension is a deadly killer because physicians don't know how to best monitor it. AND BECAUSE WE CLEARLY DO NOT TREAT IT AGGRESSIVELY. HOW MANY PHYSICIAN GIVE CIALIS TO THEIR PATIENT FOR PULMONARY HYPERTENSION? If you raise your hand, you are my hero!
The point is that by misnaming the PDGF, people will assume Aspirin would be the more likely inhibitor. Think again. There are almost 20 inhibitors of PDGF listed on the SELLECHEM list. Believe me it starts with Nexavar and Sutent. Aspirin is not on the list!
HOW MANY PEOPLE THINK OF NEXAVAR IN THEIR TREATMENT OF SCLERODERMA, A DISEASE KNOW TO HAVE PROMINENCE OF PDGF ACTIVITY? HOW MANY ONCOLOGISTS GIVE GLEEVEC TO TREAT THEIR GLIOBLASTOMA. (CLUE, AVASTIN IS INDICATED IN REFRACTORY BRAIN DISEASE-YOU THINK AVASTIN-ANGIOGENESIS, THINK NEXAVAR, TELLS SELLECHEM).
In a short study, 11 out of 12 GLIOBLASTOMAS had amplification of PDGF. This is one of the drivers of GBM. Forget Platelet, think Mesenchymal derived growth factor, and let us put the right emphasis on this Cytokine!
====================================================
By naming this compound PDGF, the scientist who described this cytokine not only picked the wrong name,
but also sent researchers on the wrong path to understanding just how important this growth factor is. As a result, some people are probably dying because the emphasis brought by the name was not clearly defined.
First of all, PDGF does not come solely from Platelets alone. It is made by a number of cells including Muscle cells, Endothelial cells and even Macrophages.
And when you think of Platelets, Coagulation comes to mind, weakening of platelets and the like. If this PDGF does this, it is at a strictly minimal or insignificant level. The effect on Platelets is only mentioned by those who clearly have been fooled and kept looking for rare effects which eventually can be found. This PDGF works on Mesenchymal cells since creation. It participates in Embryogenesis, cell survival, proliferation, angiogenesis and differentiation. In adults, its main effect is on Fibroblast and Glial cells.
When you think Platelet, platelet Aggregation, adhesion and so forth. PDGF kills by Fibrosis in cirrhosis of the liver and Pulmonary hypertension, one of the worse silent killers of our time. Pulmonary Hypertension is a deadly killer because physicians don't know how to best monitor it. AND BECAUSE WE CLEARLY DO NOT TREAT IT AGGRESSIVELY. HOW MANY PHYSICIAN GIVE CIALIS TO THEIR PATIENT FOR PULMONARY HYPERTENSION? If you raise your hand, you are my hero!
The point is that by misnaming the PDGF, people will assume Aspirin would be the more likely inhibitor. Think again. There are almost 20 inhibitors of PDGF listed on the SELLECHEM list. Believe me it starts with Nexavar and Sutent. Aspirin is not on the list!
HOW MANY PEOPLE THINK OF NEXAVAR IN THEIR TREATMENT OF SCLERODERMA, A DISEASE KNOW TO HAVE PROMINENCE OF PDGF ACTIVITY? HOW MANY ONCOLOGISTS GIVE GLEEVEC TO TREAT THEIR GLIOBLASTOMA. (CLUE, AVASTIN IS INDICATED IN REFRACTORY BRAIN DISEASE-YOU THINK AVASTIN-ANGIOGENESIS, THINK NEXAVAR, TELLS SELLECHEM).
In a short study, 11 out of 12 GLIOBLASTOMAS had amplification of PDGF. This is one of the drivers of GBM. Forget Platelet, think Mesenchymal derived growth factor, and let us put the right emphasis on this Cytokine!
Monday, January 28, 2013
ASCO GI: Phase III Bevacizumab Results of the AVEX and TRIBE Trials
ASCO GI: Phase III Bevacizumab Results of the AVEX and TRIBE Trials
Plus: Avastin gets new indication from FDA for second-line treatment
By Anna Azvolinsky, PhD1 |
January 28, 2013
1Freelance Science Writer and Cancer Network Contributor. Follow Her on Twitter 
The same week that bevacizumab (Avastin) received a new indication
for the treatment of metastatic colorectal cancer, results from two
phase III trials involving the drug were presented at the American
Society of Clinical Oncology 2013 Gastrointestinal Cancers Symposium
(ASCO GI) held January 24–26 in San Francisco.
Among 35 Italian centers, 508 patients
were randomized one to one to either arm, which both included up to 12
cycles of 5 mg/kg bevacizumab followed by bevacizumab plus fluorouracil
as a maintenance therapy.
The study met its primary endpoint—a median progression-free survival of 11.9 months was seen in the FOLFOXIRI arm compared with 9.5 months in the FOLFIRI arm (hazard ratio [HR] = 0.72; P = .001). Response rates were also higher for the FOLFOXIRI combination—64% compared with 53% in the FOLFIRI group (P = .015). Toxicities were as expected and comparable in the two groups.
According to the study researchers, this is the first randomized, prospective trial that has analyzed the benefit of bevacizumab specifically in elderly patients. The results show the combination may be a better treatment that improves elderly patient outcomes. The results validate the use of bevacizumab with capecitabine, a fluoropyrimidine, in elderly patients.
“[These results] confirm a benefit with increased response and tumor control,” said David Cunningham, MD, head of the gastrointestinal unit at the Royal Marsden Hospital in the United Kingdom, and the presenter of the study.
The open-label trial administered bevacizumab to one half of the patients at a 7.5 mg/kg dose every 3 weeks. A total of 280 patients (median age of 76) in 10 countries were part of the trial, which showed the combination prolonged progression-free survival compared with chemotherapy alone. Progression-free survival was 9.1 months for patients taking the combination compared with 5.1 months in the chemotherapy alone arm (HR = 0.53; P < .001).
Overall survival was also improved, but the difference between the two arms was not statistically significant—median overall survival was 20.7 months in the combination arm compared with 16.8 months for the capecitabine arm (HR = 0.79; P = .182). Grade 3 and higher adverse events were more frequent in the combination arm, but researchers said the regimen was generally well tolerated. Grade 3 or higher toxicities were seen in 59% of patients taking bevacizumab plus capecitabine compared with 44.1% of patients taking capecitabine alone.
“This trial result emphasizes that with appropriate selection, patients with advanced colorectal cancer, regardless of age, may benefit from chemotherapy and that the combination of capecitabine and bevacizumab represents a good option that has a favorable balance between efficacy against side effects,” said Cunningham.
Patients receiving the combination lived longer compared with those who switched to chemotherapy alone as a second-line treatment. Results showed a 19% risk of death reduction for patients on the combination therapy compared with standard chemotherapy alone (HR = 0.81; P = .0057) in the phase III ML18147 trial. The median overall survival was 11.2 months compared with 9.8 months. The results are published in the Lancet Oncology.
Bevacizumab is already approved in combination with chemotherapy as a first-line therapy for metastatic colorectal cancer patients and also as a second-line treatment in combination with FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin).
TRIBE Trial Results at ASCO GI 2013
Results of the phase III TRIBE trial—comparing bevacizumab plus FOLFOXIRI with bevacizumab plus FOLFIRI—for metastatic colorectal cancer patients who have not been previously treated with chemotherapy were presented at ASCO GI (abstract #336). First-line FOLFOXIRI combined with bevacizumab showed better efficacy compared with the combination with FOLFIRI. A phase II trial had initially showed promise of this combination.The study met its primary endpoint—a median progression-free survival of 11.9 months was seen in the FOLFOXIRI arm compared with 9.5 months in the FOLFIRI arm (hazard ratio [HR] = 0.72; P = .001). Response rates were also higher for the FOLFOXIRI combination—64% compared with 53% in the FOLFIRI group (P = .015). Toxicities were as expected and comparable in the two groups.
AVEX Trial Results at ASCO GI 2013
Another bevacizumab phase III trial reported at the meeting was the AVEX trial of elderly metastatic colorectal cancer patients. The AVEX trial compared bevacizumab in combination with capecitabine or capecitabine alone in previously untreated patients 70 years or older (abstract #337).According to the study researchers, this is the first randomized, prospective trial that has analyzed the benefit of bevacizumab specifically in elderly patients. The results show the combination may be a better treatment that improves elderly patient outcomes. The results validate the use of bevacizumab with capecitabine, a fluoropyrimidine, in elderly patients.
“[These results] confirm a benefit with increased response and tumor control,” said David Cunningham, MD, head of the gastrointestinal unit at the Royal Marsden Hospital in the United Kingdom, and the presenter of the study.
The open-label trial administered bevacizumab to one half of the patients at a 7.5 mg/kg dose every 3 weeks. A total of 280 patients (median age of 76) in 10 countries were part of the trial, which showed the combination prolonged progression-free survival compared with chemotherapy alone. Progression-free survival was 9.1 months for patients taking the combination compared with 5.1 months in the chemotherapy alone arm (HR = 0.53; P < .001).
Overall survival was also improved, but the difference between the two arms was not statistically significant—median overall survival was 20.7 months in the combination arm compared with 16.8 months for the capecitabine arm (HR = 0.79; P = .182). Grade 3 and higher adverse events were more frequent in the combination arm, but researchers said the regimen was generally well tolerated. Grade 3 or higher toxicities were seen in 59% of patients taking bevacizumab plus capecitabine compared with 44.1% of patients taking capecitabine alone.
“This trial result emphasizes that with appropriate selection, patients with advanced colorectal cancer, regardless of age, may benefit from chemotherapy and that the combination of capecitabine and bevacizumab represents a good option that has a favorable balance between efficacy against side effects,” said Cunningham.
Avastin Gets New FDA Indication for Second-Line Treatment
The US Food and Drug Administration (FDA) approved the use of bevacizumab (Avastin) as part of a new combination treatment for the second-line treatment of metastatic colorectal cancer. The drug is now approved in combination with a fluoropyrimidine-based irinotecan or oxaliplatin chemotherapy for metastatic colorectal cancer patients whose cancer has progressed after first-line treatment with a regimen that contains bevacizumab (ie, second-line treatment of bevacizumab/oxaliplatin for patients who received prior therapy of bevacizumab/irinotecan and vice versa).Patients receiving the combination lived longer compared with those who switched to chemotherapy alone as a second-line treatment. Results showed a 19% risk of death reduction for patients on the combination therapy compared with standard chemotherapy alone (HR = 0.81; P = .0057) in the phase III ML18147 trial. The median overall survival was 11.2 months compared with 9.8 months. The results are published in the Lancet Oncology.
Bevacizumab is already approved in combination with chemotherapy as a first-line therapy for metastatic colorectal cancer patients and also as a second-line treatment in combination with FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin).
Wednesday, December 19, 2012
THIORIDAZINE, A PHENOTHIAZINE WHICH IS AN INHIBITOR OF CALMODULIN WILL HAVE ANTITUMOR EFFECT AS DEMONSTRATED BY CANADIAN RESEARCHERS WHEN THEY DESCRIBED A 50 PERCENT DECREASE OF STEM CELLS. WE AT CRBCM BELIEVE THIS EFFECT IS OF COURSE LINKED TO THE RELEASE OF CALCIUM IN THE CYTOSOL LEADING TO ENDONUCLEASE STIMULATION WITH THE RESULTING ATTACK ON DNA.
THE FACT IS THIS EFFECT WILL BE MORE ON MEMBRANE WHERE CALMODULIN IS MOSTLY LOCATED. THEREFORE LIBERATION OF CALCIUM AFFECTS ELECTRICAL POLARITY AT THE MEMBRANE. TORSADE DE POINTE CAN RESULT AND HAD LED TO THE BANNING OF THIORIDAZINE IN CANADA.
THIORIDAZINE ACTS ALSO AS AN ANTIGROWTH FACTOR IN GENERAL. THIS FACT COULD CONTRIBUTE TO ITS ANTI-CANCER ACTIVITY. IN OUR PREVIOUS NOTES, WE
HAD SUGGESTED ADDING THE ANTI-CALMODULIN TO AVASTIN AS A STRATEGY TO TREAT RECURRENT BRAIN TUMOR.
THE FACT IS THIS EFFECT WILL BE MORE ON MEMBRANE WHERE CALMODULIN IS MOSTLY LOCATED. THEREFORE LIBERATION OF CALCIUM AFFECTS ELECTRICAL POLARITY AT THE MEMBRANE. TORSADE DE POINTE CAN RESULT AND HAD LED TO THE BANNING OF THIORIDAZINE IN CANADA.
THIORIDAZINE ACTS ALSO AS AN ANTIGROWTH FACTOR IN GENERAL. THIS FACT COULD CONTRIBUTE TO ITS ANTI-CANCER ACTIVITY. IN OUR PREVIOUS NOTES, WE
HAD SUGGESTED ADDING THE ANTI-CALMODULIN TO AVASTIN AS A STRATEGY TO TREAT RECURRENT BRAIN TUMOR.
Saturday, November 24, 2012
Sons of the Sevenless
SONS OF THE SEVENLESS/Hypothesis for cancer Research
As we move forward here at CRBCM, we are increasingy fond of one line of molecules;
first because of their name, and because we believe that their inhibitors could be the answer to the resistance
to some of the medications already in our armamentarium, namely Avastin, Imatinib and Herceptin. We believe that the Sons of The Sevenless which are regulator molecules switching on RAS would break resistance to Tyrosine Kinase resistance. Sons of the Sevenless, what a name! But don't you remember they say: "KILL THE SWITCH" AND DARK WILL COME. THE SWITCH IS THE SONS OF THE SEVENLESS...BASAL CELL CANCER OF THE BREAST, THE CRBCM IS AFTER YOU...SINCE THE SUGGESTION THAT BASAL CELL CANCER OF THE BREAST IS LIKE OVARIAN CANCER BY ITS GENOME. MARK MY WORD: KILLING THE SONS OF THE SEVENLESS OR KILLING THE SWITCH IS THE KEY TO TREATMENT.
ADDING TAXANE (or better yet an Anti-Kinesin) AFTER KILLING THE SWITCH (SONS OF THE SEVENLESS) WILL TURN ON THE MITOCHONDRIAL CASPASE BY AN INHERENT REFLEX MECHANISM WHICH WILL BYPASS BCL-2. THAT'S HOW YOU LEAD TO CANCER CURE!
OH BY THE WAY, ADDING STELAZINE TO AVASTIN MAY JUST DO THE TRICK FOR RECURRENT BRAIN TUMORS TOO. IT IS AN ANTI-CALMODULIN AFTER ALL!
RESEARCH IS ON AT CRBCM.
As we move forward here at CRBCM, we are increasingy fond of one line of molecules;
first because of their name, and because we believe that their inhibitors could be the answer to the resistance
to some of the medications already in our armamentarium, namely Avastin, Imatinib and Herceptin. We believe that the Sons of The Sevenless which are regulator molecules switching on RAS would break resistance to Tyrosine Kinase resistance. Sons of the Sevenless, what a name! But don't you remember they say: "KILL THE SWITCH" AND DARK WILL COME. THE SWITCH IS THE SONS OF THE SEVENLESS...BASAL CELL CANCER OF THE BREAST, THE CRBCM IS AFTER YOU...SINCE THE SUGGESTION THAT BASAL CELL CANCER OF THE BREAST IS LIKE OVARIAN CANCER BY ITS GENOME. MARK MY WORD: KILLING THE SONS OF THE SEVENLESS OR KILLING THE SWITCH IS THE KEY TO TREATMENT.
ADDING TAXANE (or better yet an Anti-Kinesin) AFTER KILLING THE SWITCH (SONS OF THE SEVENLESS) WILL TURN ON THE MITOCHONDRIAL CASPASE BY AN INHERENT REFLEX MECHANISM WHICH WILL BYPASS BCL-2. THAT'S HOW YOU LEAD TO CANCER CURE!
OH BY THE WAY, ADDING STELAZINE TO AVASTIN MAY JUST DO THE TRICK FOR RECURRENT BRAIN TUMORS TOO. IT IS AN ANTI-CALMODULIN AFTER ALL!
RESEARCH IS ON AT CRBCM.
Sunday, October 21, 2012
Clinical Hypothesis in research, prevention and Commercialization Hypothesis in cancer therapeutics
Following our first article of October 14th, we believe it is time to suggest a second hypothesis
in therapeutic research in Cancer. The early years of cancer treatment, the objective was to blast the cancer cells with chemotherapy that was in our arsenal. Most of the time this approach was able to kill the cells partially. The cancer cells quickly however learned to escape the blast, creating wonderful resistance mechanisms. As we progress in molecular biology, we are increasingly shying away from these blast approaches, leaning more and more in identifying metabolic pathways, and identifying targets in that pathway and aiming our gun and shoot it, and see what happens. This is called Target Therapy.
One pathway that we have learned a bit about is the P53 ( and down the line the pathway the Rb which lead to cell stopping in the cell cycle to allow genetic repair). This pathway is mostly triggered by an abnormality in the gene.
Today, we go back to the blast approach when we have no good Target therapy option. In fact we always try to add the target therapy to the blast chemotherapy to see if we could have the most from our money.
combination of Avastin (a target therapy) to chemotherapy is standard therapy in the United states for stage IV Colon cancer. We know that chemotherapy mostly affect our gene. This change in gene should trigger the activation of our P53 system to stop the cancer cell in its track for growth. The question now is should we give chemotherapy in patient who has an altered P53 system. What is the benefit the gene with chemotherapy, if the system that should be triggered to clean up is out.
Hypothesis:
Altered P53 pathway predict a failure of chemotherapy which has gene disturbance as main effect.
second hypothesis: preservation of status of the wild type P53 during chemotherapy may predict for a successful chemotherapy treatment (Cisplatin).
if it is true, commercialization is possible...
Don't be shy, give me your opinion!
in therapeutic research in Cancer. The early years of cancer treatment, the objective was to blast the cancer cells with chemotherapy that was in our arsenal. Most of the time this approach was able to kill the cells partially. The cancer cells quickly however learned to escape the blast, creating wonderful resistance mechanisms. As we progress in molecular biology, we are increasingly shying away from these blast approaches, leaning more and more in identifying metabolic pathways, and identifying targets in that pathway and aiming our gun and shoot it, and see what happens. This is called Target Therapy.
One pathway that we have learned a bit about is the P53 ( and down the line the pathway the Rb which lead to cell stopping in the cell cycle to allow genetic repair). This pathway is mostly triggered by an abnormality in the gene.
Today, we go back to the blast approach when we have no good Target therapy option. In fact we always try to add the target therapy to the blast chemotherapy to see if we could have the most from our money.
combination of Avastin (a target therapy) to chemotherapy is standard therapy in the United states for stage IV Colon cancer. We know that chemotherapy mostly affect our gene. This change in gene should trigger the activation of our P53 system to stop the cancer cell in its track for growth. The question now is should we give chemotherapy in patient who has an altered P53 system. What is the benefit the gene with chemotherapy, if the system that should be triggered to clean up is out.
Hypothesis:
Altered P53 pathway predict a failure of chemotherapy which has gene disturbance as main effect.
second hypothesis: preservation of status of the wild type P53 during chemotherapy may predict for a successful chemotherapy treatment (Cisplatin).
if it is true, commercialization is possible...
Don't be shy, give me your opinion!
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