1. Identifying best chemotherapy drugs in patients with Mutation in the NOTCH pathway?
Taxotere?
association with Her-2 overexpression and use of Herceptin
NF-kB blocker
or AKT blocker.
Histone de-acetylator
2. Understanding the patterns of Metastasis between epithelial (squamous) (more local recurrence) Vs AdenoCA (more distant recurrence in Esophageal cancer? Genes at play.
Does mesenchymalization dictate or drive long distance metastasis?
3. Mitomycin in NFKB amplification/Mutations
Showing posts with label taxotere. Show all posts
Showing posts with label taxotere. Show all posts
Tuesday, November 5, 2013
Tuesday, April 9, 2013
In a retrospective review of Lung cancers , use of Beta blockers may provide survival advantage
*In a retrospective review of Lung cancers , use of Beta blockers may provide survival advantage.
*Ruloxitinib, still the success story in JAK driven diseases. For JAK driven disease to be seen more in Hematologic malignancy, the receptors for hematologic growth hormones must be stimulated.
COMFORT-1 showed 41.9% of patients on Ruxolitinib had spleen reduction but in COMFORT-2, only 28% had spleen reduction by week 48.
The JAK inhibitors are now being tried in Pancreatic cancers!
*Obstruction to Cure is not only found in limitation of progress in science, but in man made complications such disparities in funding availability and managed care obstruction to access to known medications! Cure escapes us for our own doing, in a summary!
*In Breast Cancer, Inhibitors to CD4,6 are proving to be a new approach when given with Letrozole
*In Prostate cancer don't be too eager to use Steroids with enzalutmide. Steroids may "activate androgen receptors promoting the cancer". I should confess this point is a bit controversial since that's what we do, stimulate to better kill with chemotherapy (Taxotere-Cabazitaxel). But the logic may not work for another hormone used for killing.
*In Tivo-1,
they found no survival advantage for TIVOZANIB Vs Sorafenib in patient with Renal Cancer.
Tivozanib is said to be more potent and selective for VEGF receptors! PFS was superior though with TIVO!
*Check this out! The global multikinase inhibitor Regorafenib (blocks VEGFR1,KIT,TIE2,PDGFR and RET) got approved for GIST. patients received 160 mg PO daily x21 Q28. Watch for fatigue hand foot sundrome diarrhea, loss of appetite,HTN,weight loss,rash and fever. and being an anti-VEGF, bleeding and intestinal perforation of course! rare cases of Coronary attacks!
*New kid on the block, RAMUCIRUMAB TRIED IN GASTRIC CANCER!
(READ TARGETED THERAPY NEWS)
*Ruloxitinib, still the success story in JAK driven diseases. For JAK driven disease to be seen more in Hematologic malignancy, the receptors for hematologic growth hormones must be stimulated.
COMFORT-1 showed 41.9% of patients on Ruxolitinib had spleen reduction but in COMFORT-2, only 28% had spleen reduction by week 48.
The JAK inhibitors are now being tried in Pancreatic cancers!
*Obstruction to Cure is not only found in limitation of progress in science, but in man made complications such disparities in funding availability and managed care obstruction to access to known medications! Cure escapes us for our own doing, in a summary!
*In Breast Cancer, Inhibitors to CD4,6 are proving to be a new approach when given with Letrozole
*In Prostate cancer don't be too eager to use Steroids with enzalutmide. Steroids may "activate androgen receptors promoting the cancer". I should confess this point is a bit controversial since that's what we do, stimulate to better kill with chemotherapy (Taxotere-Cabazitaxel). But the logic may not work for another hormone used for killing.
*In Tivo-1,
they found no survival advantage for TIVOZANIB Vs Sorafenib in patient with Renal Cancer.
Tivozanib is said to be more potent and selective for VEGF receptors! PFS was superior though with TIVO!
*Check this out! The global multikinase inhibitor Regorafenib (blocks VEGFR1,KIT,TIE2,PDGFR and RET) got approved for GIST. patients received 160 mg PO daily x21 Q28. Watch for fatigue hand foot sundrome diarrhea, loss of appetite,HTN,weight loss,rash and fever. and being an anti-VEGF, bleeding and intestinal perforation of course! rare cases of Coronary attacks!
*New kid on the block, RAMUCIRUMAB TRIED IN GASTRIC CANCER!
(READ TARGETED THERAPY NEWS)
Wednesday, February 20, 2013
A PEEK INTO THE FUTURE!
The article published in the Lancet about Taxotere combined to Selumetinib in 2nd line treatment of lung cancer, opens the door to future therapy to come. It marks the increasing trend of incorporating Target therapy to standard good old chemotherapy. Selumetinib is a MEK inhibitor downstream from KRAS.
Already the results are impressive with the doubling of progression free survival and Overall survival.
Already, we have a peek to a new set of toxicity because these are new combinations and the outlook is grim now with almost half of the patients having Nausea, diarrhea, severe Neutropenia and stomatitis.
Not only is MEK down stream from RAS-RAF-MEK-ERK (MAPK) signaling pathway; it is the revolving door between epidermal presentation which should block Metastatic spread and Endodermal transformation that the Cancer chooses to metastasize.
Another question that will rise immediately is if we have a driver mutation, when should we stop inhibiting such target, when do we stop closing this revolving door? The rising need of maintenance therapy follows. In lung cancer, Alimta, Tarceva and Taxotere have all shown to be beneficial in maintenance setting. So the choice here would be Taxotere maintenance, or should we continue to push closed MEK with Selumetinib?
This article emphasized the fact that this was the first time that KRAS was used as a biomarker for Target therapy. Very true, but mesenchymal transformation and angiogenesis play a role in almost every cancer.
THE FIGHT IS ON.
(LAST POINT: WE HAVE NOT LEARNED ENOUGH ABOUT HOW TO PREVENT THESE SIDE EFFECTS, WE NEED TO STEP UP!)
The article published in the Lancet about Taxotere combined to Selumetinib in 2nd line treatment of lung cancer, opens the door to future therapy to come. It marks the increasing trend of incorporating Target therapy to standard good old chemotherapy. Selumetinib is a MEK inhibitor downstream from KRAS.
Already the results are impressive with the doubling of progression free survival and Overall survival.
Already, we have a peek to a new set of toxicity because these are new combinations and the outlook is grim now with almost half of the patients having Nausea, diarrhea, severe Neutropenia and stomatitis.
Not only is MEK down stream from RAS-RAF-MEK-ERK (MAPK) signaling pathway; it is the revolving door between epidermal presentation which should block Metastatic spread and Endodermal transformation that the Cancer chooses to metastasize.
Another question that will rise immediately is if we have a driver mutation, when should we stop inhibiting such target, when do we stop closing this revolving door? The rising need of maintenance therapy follows. In lung cancer, Alimta, Tarceva and Taxotere have all shown to be beneficial in maintenance setting. So the choice here would be Taxotere maintenance, or should we continue to push closed MEK with Selumetinib?
This article emphasized the fact that this was the first time that KRAS was used as a biomarker for Target therapy. Very true, but mesenchymal transformation and angiogenesis play a role in almost every cancer.
THE FIGHT IS ON.
(LAST POINT: WE HAVE NOT LEARNED ENOUGH ABOUT HOW TO PREVENT THESE SIDE EFFECTS, WE NEED TO STEP UP!)
Wednesday, January 9, 2013
FOR THE CURE, TIME FOR PARADIGM SHIFT AND A REVOLUTION AGAINST SOME OF OUR LEADERS IN CANCER MEDICINE
Cancer is a disease involving the cell. Our current understanding is that during the course of our lives, somewhere in our system, a cell's function will be altered enough to transform a normal cell into A CANCER CELL. Our current understanding is that all cells want to stay alive and for cancer cell multiplication and dissemination it appears to be assurance of a type of cell preservation. We know that to survive, the cancer cell will escape several mechanisms. How to stimulate its growth, how to escape detection by the immune system and removal by the Macrophages and related natural measures, how to stay awake by lighting up certain pathways, how to resist against external chemical attacks, how to repair damages caused by attacks, how to survive on their own etc.?
We also know that cancer cells are not the same not only by tissue of origin, but also by pathways driving them. We know that to escape death, the cancer cell uses redundancies and loopholes in its pathways, that is it may alter or multiply these pathways to overrun incoming inhibitions. It may amplify measures to block our reach toward programmed death. The cancer cell knows that once programmed death mechanisms are started, it has to die. It builds things like Bcl-2 around the Caspase death path. The cancer cell knows that there are inhibitory forces that need to be altered. P53 is one of the Major forces. It needs to be altered or mutated. Flow through a pathway is another force. And altering regulators may be one way to control the flow. Or leaving a switch on to drive the pathways. etc...
We also know that every major target in pathways has effects downstream toward the nucleus and its DNA, and upstream toward the Membrane. For some, we have found lateral connections serving as loophole escape. More than one phenotype of an important Target is meant to provide Resistance to attacks of the main type.
With chemotherapy, we have had some success. Our failures reside in the mechanisms of resistance, in the ability of the cancer cell to repair itself and escape death. Escaping death appears to be also solely linked to protection against Necrosis and programmed death.
We also know about Driver pathways as well as forces we can use to stop cell migration, division and seeding. We have got to use this knowledge to plan our action for the cure.
The success of target therapy needs to tell us that leaders who continue to push chemotherapy as the only alternative, creating more combinations, need to be more and more left alone, while we switch to Targeting therapy and some combination therapies.
Targeting therapy tells us we got to get better at defining Driver pathways to be effective. Particularly in solid tumors. This is the major priority. HOW DO YOU TELL THIS IS A DRIVER TARGET OR PATHWAY? IS IT BY DOSING REGULATORY MOLECULES, ENZYMES ALONG A PATHWAY, LEVEL OF TRANSCRIPTION GENES, STATUS OF SWITCH TO TARGET MOLECULES, PROMOTER EXPRESSION? HOW DO YOU SAY THIS IS THE DRIVER PATHWAY? WITH THIS KNOWLEDGE WE CAN AVOID STUDIES LIKE TAXOTERE & REVLIMID IN PROSTATE CANCER, WHEN TAXOTERE & VELCADE WOULD HAVE BEEN BETTER.
IF WE KNOW HOW TO DO THIS, OUR PATH TO CURE IS ASSURED.
The second question: HOW TO GET THIS CELL TO CASPASE, TO LYSOZOMAL HYDROLASES AND CATHEPSINS, AND OTHER NECROTIC AND AUTOPHAGIC PROCESSES? HOW TO PUSH IT TO PROGRAMMED DEATH?
TIME TO WAKE UP AND SMELL THE COFFEE BEFORE ANOTHER RUN FOR THE CURE!
We also know that cancer cells are not the same not only by tissue of origin, but also by pathways driving them. We know that to escape death, the cancer cell uses redundancies and loopholes in its pathways, that is it may alter or multiply these pathways to overrun incoming inhibitions. It may amplify measures to block our reach toward programmed death. The cancer cell knows that once programmed death mechanisms are started, it has to die. It builds things like Bcl-2 around the Caspase death path. The cancer cell knows that there are inhibitory forces that need to be altered. P53 is one of the Major forces. It needs to be altered or mutated. Flow through a pathway is another force. And altering regulators may be one way to control the flow. Or leaving a switch on to drive the pathways. etc...
We also know that every major target in pathways has effects downstream toward the nucleus and its DNA, and upstream toward the Membrane. For some, we have found lateral connections serving as loophole escape. More than one phenotype of an important Target is meant to provide Resistance to attacks of the main type.
With chemotherapy, we have had some success. Our failures reside in the mechanisms of resistance, in the ability of the cancer cell to repair itself and escape death. Escaping death appears to be also solely linked to protection against Necrosis and programmed death.
We also know about Driver pathways as well as forces we can use to stop cell migration, division and seeding. We have got to use this knowledge to plan our action for the cure.
The success of target therapy needs to tell us that leaders who continue to push chemotherapy as the only alternative, creating more combinations, need to be more and more left alone, while we switch to Targeting therapy and some combination therapies.
Targeting therapy tells us we got to get better at defining Driver pathways to be effective. Particularly in solid tumors. This is the major priority. HOW DO YOU TELL THIS IS A DRIVER TARGET OR PATHWAY? IS IT BY DOSING REGULATORY MOLECULES, ENZYMES ALONG A PATHWAY, LEVEL OF TRANSCRIPTION GENES, STATUS OF SWITCH TO TARGET MOLECULES, PROMOTER EXPRESSION? HOW DO YOU SAY THIS IS THE DRIVER PATHWAY? WITH THIS KNOWLEDGE WE CAN AVOID STUDIES LIKE TAXOTERE & REVLIMID IN PROSTATE CANCER, WHEN TAXOTERE & VELCADE WOULD HAVE BEEN BETTER.
IF WE KNOW HOW TO DO THIS, OUR PATH TO CURE IS ASSURED.
The second question: HOW TO GET THIS CELL TO CASPASE, TO LYSOZOMAL HYDROLASES AND CATHEPSINS, AND OTHER NECROTIC AND AUTOPHAGIC PROCESSES? HOW TO PUSH IT TO PROGRAMMED DEATH?
TIME TO WAKE UP AND SMELL THE COFFEE BEFORE ANOTHER RUN FOR THE CURE!
Wednesday, December 19, 2012
COMBINATION OF XELODA, AND ANTICALMODULIN AND AN ANTI-P35 ANTIBODY FOR TRIPLE NEGATIVE BREAST CANCER.,
OR TAXOTERE-XELODA-VELCADE-ANTI-P35
If the fighting cancer strategy is to disrupt the cell where it hurts the most, the above combinations make the most sense. These combinations achieve the following:
1. Disruption of Microfilaments/Microtubules which in turn disrupt Anaphases in dividing cancer cells. This also disrupts membrane attachment of Cytochromes in Mitochondria by disrupting the Cytoskeleton, and leads to Caspase release.
2. Xeloda leads to an increase of intracellular 5-FU and to DNA breakage which triggers activation of P53 induced stoppage of cell division.
3. The Anti-Calmodulin will add and increase an intracellular release of Calcium leading to stimulation of Endonucleases which will further damage the DNA.
4. The Anti-P35 decreases resistance to Caspases since P35 is an inhibitor of Caspases.
5. To lead to growth advantage, most cancers get a mutation of the MDM2 which leads to increased ubiquitination proteins/cyclins favorable to apoptosis, making Velcade a powerful drug as it disrupts the proteasomes!
With these combinations, we are trying to harvest the strongest destructive forces in a cell!
OR TAXOTERE-XELODA-VELCADE-ANTI-P35
If the fighting cancer strategy is to disrupt the cell where it hurts the most, the above combinations make the most sense. These combinations achieve the following:
1. Disruption of Microfilaments/Microtubules which in turn disrupt Anaphases in dividing cancer cells. This also disrupts membrane attachment of Cytochromes in Mitochondria by disrupting the Cytoskeleton, and leads to Caspase release.
2. Xeloda leads to an increase of intracellular 5-FU and to DNA breakage which triggers activation of P53 induced stoppage of cell division.
3. The Anti-Calmodulin will add and increase an intracellular release of Calcium leading to stimulation of Endonucleases which will further damage the DNA.
4. The Anti-P35 decreases resistance to Caspases since P35 is an inhibitor of Caspases.
5. To lead to growth advantage, most cancers get a mutation of the MDM2 which leads to increased ubiquitination proteins/cyclins favorable to apoptosis, making Velcade a powerful drug as it disrupts the proteasomes!
With these combinations, we are trying to harvest the strongest destructive forces in a cell!
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