AGE RELATED EXPRESSION OF DEFICIENT GENE
Although one may have deficient gene,death from its consequences varies based on how critical lack of expression is to the body. Lack of function in a critical tissue leads rapidly to death. Expression of a deficient gene depends on whether it it dominant or recessive, and whether one is homo or heterozygotic as related to the gene in question. many diseases of genetic basis express themselves at a letter stage in life. Polycystic Kidney disease for example gives its full blown syndrome only after 30 years of age, and starts worsening to finally take the life of the bearesr in their 5th ot sixth decade of life. Althto though one cannot say for sure what intervened with age for the syndrome to fully express, we know that immune and hormonal developments contribute significantly to this unfortunate unfolding.
We know that in infectious processes we encounter as we age, there is disturbances of Interferons levels, and if one has an autoimmune disease, these interferon levelsare somewhat permanent or constant. Interferon activate T cell and boost Immunity but also secondarily immune system surveillance of cancer occurrence. This interferon seems linked to Class I histocompatibilty HLA-A,B,C.
In Women however, as they age and enter reproductive age, there is need to suppress class I HLAin order to "tolerate" a child/fetus. It is assumed that a vague of hormone driven gene methylation seems to be the mechanism. Gene methylation will silence many genes and could potentially silence normal genes that where conterbalancing the gene defect. Defectuous genes will this way get there chance to finally express themselves and cause progression of syndromes thay can cause. Androgenic development in males achieves the same deterioration. Giving Azacytidine had reversed these methylation by the way although clinical trials are still ongoing on whetehr it can meaningfully change the course of these gene based diseases.That is before irreversible tissue damage sets in.
Thursday, June 6, 2013
Wednesday, June 5, 2013
CRK GENE
It is a co-factor to many Kinases, and sometime act as a regulator
CRK (gene) has been shown to interact with:
It is a co-factor to many Kinases, and sometime act as a regulator
CRK (gene) has been shown to interact with:
- BCAR1,[7][8][9][10][11][12][13][14][15]
- Cbl gene,[16][17]
- Dock180,[18][9][10][19][20]
- EPS15,[21]
- Epidermal growth factor receptor,[22][23]
- Grb2,[24][18][25] (A WILD WILD GENE)
The focal adhesion kinase (FAK), a protein-tyrosine kinase (PTK), associates with integrin receptors and is activated by cell binding to extracellular matrix proteins, such as fibronectin (FN). FAK autophosphorylation at Tyr-397 promotes Src homology 2 (SH2) domain binding of Src family PTKs, and c-Src phosphorylation of FAK at Tyr-925 creates an SH2 binding site for the Grb2 SH2-SH3 adaptor protein. FN-stimulated Grb2 binding to FAK may facilitate intracellular signaling to targets such as ERK2-mitogen-activated protein kinase. We examined FN-stimulated signaling to ERK2 and found that ERK2 activation was reduced 10-fold in Src- fibroblasts, compared to that of Src- fibroblasts stably reexpressing wild-type c-Src. FN-stimulated FAK phosphotyrosine (P.Tyr) and Grb2 binding to FAK were reduced, whereas the tyrosine phosphorylation of another signaling protein, p130cas, was not detected in the Src- cells. - IRS4,[26][27]
- MAP4K1,[28][29][30]
- MAPK8,[31]
- NEDD9,[32][33]
- PDGFRA,[34][35]
- PDGFRB,[34]
- PTK2,[9][12]
- Paxillin[12][36]
- RAPGEF1,[37]
- RICS,[38][39]
- SH3KBP1,[40] and
- SOS1.[25]wikipedia
- Crk together with CrkL participates in the Reelin signaling cascade downstream of DAB1.[2][3]
- We could get your attention that REELIN defect leads to brain MALFORMATION, POINTING TO CRK AND DAB1 AS IMPORTANT TARGET GENES IN SARCOMA!
-
Reelin is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates synaptic plasticity by enhancing the induction and maintenance of long-term potentiation.[2][3] It also stimulates dendrite[4] and dendritic spine[5] development and regulates the continuing migration of neuroblasts generated in adult neurogenesis sites like subventricular and subgranular zones. It is found not only in the brain, but also in the spinal cord, blood, and other body organs and tissues.
Reelin has been suggested to be implicated in pathogenesis of several brain diseases. The expression of the protein has been found to be significantly lower in schizophrenia and psychotic bipolar disorder, but the cause of this observation remains uncertain as studies show that psychotropic medication itself affects reelin expression. Moreover, the epigenetic hypothesis aimed at explaining the changed levels[6] has received some contradictory evidence.[7][8] Total lack of reelin causes a form of lissencephaly. Reelin may also play a role in Alzheimer's disease, temporal lobe epilepsy and autism.(WIKIPEDIA)
Reelin takes part in the developmental change of NMDA receptor configuration, increasing mobility of NR2B-containing receptors and thus decreasing the time they spend at the synapse.[53][dead link][54][55] It has been hypothesized that this may be a part of the mechanism behind the "NR2B-NR2A switch" that is observed in the brain during its postnatal development.[56] Ongoing reelin secretion by GABAergic hippocampal neurons is necessary to keep NR2B-containing NMDA receptors at a low level.[52]
The Disabled-1 (Dab1) gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain and during adult neurogenesis
IMPORTANT TARGET OF IMMUNOTHERAPY
MUNITIAE AT THE CELLULAR MEMBRANE
TO FIGURE OUT THE FOLLOWING EXCERPTS ONE SHOULD REMEMBER THE PHENOMENA OCCURRING DURING INJURY TO THE BLOOD VESSEL. WHEN A BLOOD VESSEL IS OPEN DURING AN INJURY, IT IS THE SUDDEN EXPOSURE OF BLOOD CELL WITH OUTSIDE TISSUE/PROTEIN (COLLAGEN) THAT TRIGGERS COAGULATION, PLATELET ACTIVATION.
NOW IMAGINE A MOLECULE OF ESTROGEN ARRIVING AT CELL SURFACE AND BINDING TO ITS RECEPTOR, 2 THINGS HAPPEN, ONE IS THAT THE LINKAGE CAUSES AN INTERNAL SIGNAL TRANSDUCTION GOING THROUGH A PATHWAY
BUT SOMETIME THE ALL RECEPTOR DETACHES WITH ITS STIMULANT AND IS INTERNALIZED. AT POINT OF DETACHEMENT, THERE IS CONTACT OF FIBRONECTIN (EXTRACELLULAR) WITH CYTOSOL CONTENT FOCAL ADHESION KINASES (fak) AND THE REST FOLLOWS (5 BULLETS)
1.the binding of a neuropeptide to its cognate GPCR triggers the activation of multiple signal transduction pathways that act in a synergistic and combinatorial fashion to relay the mitogenic signal to the nucleus and promote cell proliferation. A rapid increase in the synthesis of lipid-derived second messengers with subsequent activation of protein phosphorylation cascades is an important early response to neuropeptides. An emerging theme in signal transduction is that these agonists also induce rapid and coordinate tyrosine phosphorylation of cellular proteins including the nonreceptor tyrosine kinase p125fak and the adaptor proteins p130cas and paxillin. This tyrosine phosphorylation pathway depends on the integrity of the actin cytoskeleton and requires functional Rho.(ROZENGHURT)
THAT IS AFTER A GROWTH FACTOR HAS LINKED TO ITS RECEPTOR, COUPLING WITH A G-PROTEIN WILL TRIGGER AN EXPLOSION ON PHOSPHORYLATION IN ALL DIRECTION, ON THESE PHOSPHORYLATION HITS A KINASE OF AN IMPORTANT PATHWAY AND THE PATHWAY ENTER INTO ACTION.
2.This effect required the autophosphorylation site of FAK, which is a binding site for Src family kinases. Integrin-mediated phosphorylation of Cas was not, however, compromised in fibroblasts lacking FAK.
FAK seems not to be necessary for phosphorylation of Cas, but when autophosphorylated, FAK may recruit Src family kinases to phosphorylate Cas. Cas was found to form complexes with Src homology 2 (SH2) domain-containing signaling molecules, such as the SH2/SH3 adapter protein Crk, following integrin-induced tyrosine phosphorylation. Guanine nucleotide exchange factors C3G and Sos were found in the Cas-Crk complex upon integrin ligand binding. These observations suggest that Cas serves as a docking protein and may transduce signals to downstream signaling pathways following integrin-mediated cell adhesion.(VUORI ET AL)
3. The focal adhesion kinase (FAK), a protein-tyrosine kinase (PTK), associates with integrin receptors and is activated by cell binding to extracellular matrix proteins, such as fibronectin (FN). FAK autophosphorylation at Tyr-397 promotes Src homology 2 (SH2) domain binding of Src family PTKs, and c-Src phosphorylation of FAK at Tyr-925 creates an SH2 binding site for the Grb2 SH2-SH3 adaptor protein. FN-stimulated Grb2 binding to FAK may facilitate intracellular signaling to targets such as ERK2-mitogen-activated protein kinase. We examined FN-stimulated signaling to ERK2 and found that ERK2 activation was reduced 10-fold in Src- fibroblasts, compared to that of Src- fibroblasts stably reexpressing wild-type c-Src. FN-stimulated FAK phosphotyrosine (P.Tyr) and Grb2 binding to FAK were reduced, whereas the tyrosine phosphorylation of another signaling protein, p130cas, was not detected in the Src- cells.(SCHLAEPFER ET AL)
Src-family binding and phosphorylation of FAK at Tyr-925 creates a Grb2 SH2-domain binding site and provides a link to the activation of the Ras signal transduction pathway. In Src-transformed cells, this pathway may be constitutively activated as a result of FAK Tyr-925 phosphorylation in the absence of integrin stimulation.
4. Pyk2 overexpression enhanced FN-stimulated activation
5.RAFTK/Pyk2 is expressed mainly in the central nervous system and in cells derived from hematopoietic lineages, while FAK is widely expressed in various tissues and links transmembrane integrin receptors to intracellular pathways. This review describes the role of RAFTK/Pyk2 in various signalling cascades and details the differential signalling by FAK and RAFTK/Pyk2. of co-transfected ERK2.(AVRAHAM)
===============================================================
SO 2 MAIN ROUTES
THE ERK2
AND THE GRB2
DO REMEMBER GRB2 IS THE WILD WILD WEST OF GENES!
The N-terminal SH3 domain binds to proline-rich peptides and can bind to the Ras-guanine exchange factor SOS.
The C-terminal SH3 domain binds to peptides conforming to a P-X-I/L/V/-D/N-R-X-X-K-P motif that allows it to specifically bind to proteins such as Gab-1.[4]
MUNITIAE AT THE CELLULAR MEMBRANE
TO FIGURE OUT THE FOLLOWING EXCERPTS ONE SHOULD REMEMBER THE PHENOMENA OCCURRING DURING INJURY TO THE BLOOD VESSEL. WHEN A BLOOD VESSEL IS OPEN DURING AN INJURY, IT IS THE SUDDEN EXPOSURE OF BLOOD CELL WITH OUTSIDE TISSUE/PROTEIN (COLLAGEN) THAT TRIGGERS COAGULATION, PLATELET ACTIVATION.
NOW IMAGINE A MOLECULE OF ESTROGEN ARRIVING AT CELL SURFACE AND BINDING TO ITS RECEPTOR, 2 THINGS HAPPEN, ONE IS THAT THE LINKAGE CAUSES AN INTERNAL SIGNAL TRANSDUCTION GOING THROUGH A PATHWAY
BUT SOMETIME THE ALL RECEPTOR DETACHES WITH ITS STIMULANT AND IS INTERNALIZED. AT POINT OF DETACHEMENT, THERE IS CONTACT OF FIBRONECTIN (EXTRACELLULAR) WITH CYTOSOL CONTENT FOCAL ADHESION KINASES (fak) AND THE REST FOLLOWS (5 BULLETS)
1.the binding of a neuropeptide to its cognate GPCR triggers the activation of multiple signal transduction pathways that act in a synergistic and combinatorial fashion to relay the mitogenic signal to the nucleus and promote cell proliferation. A rapid increase in the synthesis of lipid-derived second messengers with subsequent activation of protein phosphorylation cascades is an important early response to neuropeptides. An emerging theme in signal transduction is that these agonists also induce rapid and coordinate tyrosine phosphorylation of cellular proteins including the nonreceptor tyrosine kinase p125fak and the adaptor proteins p130cas and paxillin. This tyrosine phosphorylation pathway depends on the integrity of the actin cytoskeleton and requires functional Rho.(ROZENGHURT)
THAT IS AFTER A GROWTH FACTOR HAS LINKED TO ITS RECEPTOR, COUPLING WITH A G-PROTEIN WILL TRIGGER AN EXPLOSION ON PHOSPHORYLATION IN ALL DIRECTION, ON THESE PHOSPHORYLATION HITS A KINASE OF AN IMPORTANT PATHWAY AND THE PATHWAY ENTER INTO ACTION.
2.This effect required the autophosphorylation site of FAK, which is a binding site for Src family kinases. Integrin-mediated phosphorylation of Cas was not, however, compromised in fibroblasts lacking FAK.
FAK seems not to be necessary for phosphorylation of Cas, but when autophosphorylated, FAK may recruit Src family kinases to phosphorylate Cas. Cas was found to form complexes with Src homology 2 (SH2) domain-containing signaling molecules, such as the SH2/SH3 adapter protein Crk, following integrin-induced tyrosine phosphorylation. Guanine nucleotide exchange factors C3G and Sos were found in the Cas-Crk complex upon integrin ligand binding. These observations suggest that Cas serves as a docking protein and may transduce signals to downstream signaling pathways following integrin-mediated cell adhesion.(VUORI ET AL)
3. The focal adhesion kinase (FAK), a protein-tyrosine kinase (PTK), associates with integrin receptors and is activated by cell binding to extracellular matrix proteins, such as fibronectin (FN). FAK autophosphorylation at Tyr-397 promotes Src homology 2 (SH2) domain binding of Src family PTKs, and c-Src phosphorylation of FAK at Tyr-925 creates an SH2 binding site for the Grb2 SH2-SH3 adaptor protein. FN-stimulated Grb2 binding to FAK may facilitate intracellular signaling to targets such as ERK2-mitogen-activated protein kinase. We examined FN-stimulated signaling to ERK2 and found that ERK2 activation was reduced 10-fold in Src- fibroblasts, compared to that of Src- fibroblasts stably reexpressing wild-type c-Src. FN-stimulated FAK phosphotyrosine (P.Tyr) and Grb2 binding to FAK were reduced, whereas the tyrosine phosphorylation of another signaling protein, p130cas, was not detected in the Src- cells.(SCHLAEPFER ET AL)
Src-family binding and phosphorylation of FAK at Tyr-925 creates a Grb2 SH2-domain binding site and provides a link to the activation of the Ras signal transduction pathway. In Src-transformed cells, this pathway may be constitutively activated as a result of FAK Tyr-925 phosphorylation in the absence of integrin stimulation.
4. Pyk2 overexpression enhanced FN-stimulated activation
5.RAFTK/Pyk2 is expressed mainly in the central nervous system and in cells derived from hematopoietic lineages, while FAK is widely expressed in various tissues and links transmembrane integrin receptors to intracellular pathways. This review describes the role of RAFTK/Pyk2 in various signalling cascades and details the differential signalling by FAK and RAFTK/Pyk2. of co-transfected ERK2.(AVRAHAM)
===============================================================
SO 2 MAIN ROUTES
THE ERK2
AND THE GRB2
DO REMEMBER GRB2 IS THE WILD WILD WEST OF GENES!
Function and expression
Grb2 is widely expressed and is essential for multiple cellular functions. Inhibition of Grb2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types, and so it is not surprising that a targeted gene disruption of Grb2 in mouse is lethal at an early embryonic stage. Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction.Domains
The SH2 domain of Grb2 binds to phosphorylated tyrosine-containing peptides on receptors or scaffold proteins with a preference for pY-X-N-X, where X is generally a hydrophobic residue such as valine (see [3]).The N-terminal SH3 domain binds to proline-rich peptides and can bind to the Ras-guanine exchange factor SOS.
The C-terminal SH3 domain binds to peptides conforming to a P-X-I/L/V/-D/N-R-X-X-K-P motif that allows it to specifically bind to proteins such as Gab-1.[4]
Interactions
Grb2 has been shown to interact with Arachidonate 5-lipoxygenase,[5][6] Lymphocyte cytosolic protein 2,[7][8][9][10][11] GAB2,[12][13][14] B-cell linker,[15][16][17][18] Abl gene,[19][20] CD28,[21][22] FRS2,[23][24][25][26] Mitogen-activated protein kinase 9,[27][28] CD22,[29][30] NEU3,[31] ETV6,[12] MAP2,[32][33] Dock180,[34][35] PIK3R1,[36][37] SH2B1,[38][39] CRK,[40][41][42] GAB1,[7][43][44] MST1R,[45][46] DNM1,[47][48] Huntingtin,[49] Src,[50][51] Beta-2 adrenergic receptor,[52] VAV2,[53][54] ADAM15,[55] RAPGEF1,[56][57] VAV1,[58][59][60][61] HER2/neu,[54][62][63] Epidermal growth factor receptor,[2][43][53][62][64][65][66][67][68][69] PDGFRB,[69][70][71] PTK2,[72][73][74][75][76] Erythropoietin receptor,[77][78] Linker of activated T cells,[79][80][81] Dystroglycan,[82] SH3KBP1,[83][84] Granulocyte colony-stimulating factor receptor,[85] DCTN1,[86] CDKN1B,[87] Colony stimulating factor 1 receptor,[88] EPH receptor A2,[89] KHDRBS1,[43][90][91] RET proto-oncogene,[92][93] PLCG1,[94][95][96] TrkA,[97][98] PRKAR1A,[66] Janus kinase 2,[99][100] MUC1,[101] CD117,[78][102][103] Fas ligand,[104][105] Janus kinase 1,[100][106] VAV3,[53][107] BCAR1,[73][108] PTPN1,[109][110] INPP5D,[111] ITK,[112][113] SHC1,[51][53][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132] PTPN12,[133] C-Met,[134][135] PTPN11,[71][85][127][136][137][138][139][140][141] Glycoprotein 130,[61] PTPN6,[51][136][142] Syk,[51][136] MAP4K1,[143][144][145][146] Wiskott-Aldrich syndrome protein,[147][148] NCKIPSD,[149][150] PTPRA,[151][152][153] BCR gene,[12][115][154][155][156][157] CBLB,[158][159][160] Cbl gene,[9][24][51][90][124][158][161][162][163][164][165][166][167] SOS1,[8][24][42][43][48][51][53][60][68][90][95][101][115][122][124][131][168][169][170][171][172] IRS1,[100][114][173] TNK2,[116][174] MED28,[175] MAP3K1[176] and HNRNPC.[177]
IN OTHER NEWS
*USE OF GM-CSF BOOSTS IPILIMUMAB ACTIVITY! GO FIGURE THAT...
*NO SURPRISE HERE, CLASSIII BETA-TUBULIN PREDICT GOOD RESPONSE TO TAXANE IN ER NEGATIVE BREAST CANCER
*MAKES PERFECT SENSE TO TINKLE WITH ANDROGEN RECEPTOR IN APOCRINE SUBTYPE OF CANCERS
*ONE GOOD NEGATIVE STUDY! OR IS IT? SEND COMMENTs!
Bevacizumab and erlotinib in previously untreated inoperable and metastatic hepatocellular carcinoma
Govindarajan R et al. – The 28% progression-free survival
rate at 27 weeks was not significantly higher than the recent historical
control rate of 20% observed on the placebo arm of the Sorafenib
Hepatocellular Carcinoma Assessment Randomized Protocol trial (P=0.28).
The combination of bevacizumab and erlotinib does not appear to have
sufficient efficacy in patients with unresectable and metastatic HCC not
amenable to local therapy.
*USE OF GM-CSF BOOSTS IPILIMUMAB ACTIVITY! GO FIGURE THAT...
*NO SURPRISE HERE, CLASSIII BETA-TUBULIN PREDICT GOOD RESPONSE TO TAXANE IN ER NEGATIVE BREAST CANCER
*MAKES PERFECT SENSE TO TINKLE WITH ANDROGEN RECEPTOR IN APOCRINE SUBTYPE OF CANCERS
*ONE GOOD NEGATIVE STUDY! OR IS IT? SEND COMMENTs!
Bevacizumab and erlotinib in previously untreated inoperable and metastatic hepatocellular carcinoma
American Journal of Clinical Oncology, 05/29/2013
Clinical Article
FROM PRACTICE UPDATE, ASCO NEWS
| |||||||||||||
Tuesday, June 4, 2013
HUGE NEWS FROM MEDSCAPE! PRACTICE CHANGING! IN ALL FAIRNESS GO TO MEDSCAPE FOR A FULL REPORT!
This coverage is not sanctioned by, nor a part of, the American Society of Clinical Oncology.
CHICAGO, Illinois — The common practice of
administering intravenous calcium and magnesium along with oxaliplatin
to reduce the side effect of neuropathy should be stopped, experts
say.
The first placebo-randomized phase 3 trial of this practice has shown no benefit. The results were presented here at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO®) by Charles Loprinzi, MD, from the Mayo Clinic in Rochester, Minnesota.
The trial was conducted in 353 patients with colon cancer undergoing adjuvant therapy with FOLFOX (5-fluorouracil, oxaliplatin, and leucovorin), who were randomized to receive intravenous CaMg (1g calcium gluconate, 1 mg magnesium sulfate) or placebo before and after oxaliplatin. There was also a third arm in the trial, in which patients received CaMg before and placebo after the oxaliplatin.
The results showed no differences between the groups in either acute neurotoxicity or cumulative sensory neurotoxicity, as assessed both by patient and physician questionnaires."
"Medscape Medical News from the:
Stop Using Calcium and Magnesium With Oxaliplatin
The first placebo-randomized phase 3 trial of this practice has shown no benefit. The results were presented here at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO®) by Charles Loprinzi, MD, from the Mayo Clinic in Rochester, Minnesota.
The trial was conducted in 353 patients with colon cancer undergoing adjuvant therapy with FOLFOX (5-fluorouracil, oxaliplatin, and leucovorin), who were randomized to receive intravenous CaMg (1g calcium gluconate, 1 mg magnesium sulfate) or placebo before and after oxaliplatin. There was also a third arm in the trial, in which patients received CaMg before and placebo after the oxaliplatin.
The results showed no differences between the groups in either acute neurotoxicity or cumulative sensory neurotoxicity, as assessed both by patient and physician questionnaires."
EVIDENCES MOUNT THAT UNIVERSITIES ARE COMING TOGETHER TO TAKE ALL THE MONEY FOR CANCER RESEARCH
READ FOR YOUR SELF!
BIG CANCER RESEARCH CONSORTIUM (from ONCOLOGY TIMES)
READ FOR YOUR SELF!
BIG CANCER RESEARCH CONSORTIUM (from ONCOLOGY TIMES)
CHICAGO
– In a new venture, 11 university-based matrix cancer centers are
uniting “to transform cancer research through collaborative oncology
trials that leverage the scientific and clinical expertise of the Big
Ten universities.”
The
consortium will allow universities with similar missions, visions, and
cultures to create a regional cancer team science initiative to advance
research by sharing resources and strengths to form what is hoped will
be a lean, efficient, and collaborative effort that will focus on Phase 0
to II clinical trials accruing patients with specific diseases and
molecular characteristics.
The
news releases sent out on Friday by the individual institutions all had
the same information but included no clear direction as to who was the
designated point person or spokesperson, which was perhaps in deference
to the consortium’s sensitivity to having any one institution overshadow
the others.
However,
the mention toward the end of the release that the Indianapolis-based
Hoosier Oncology Group (HOG) would serve as the administrative
headquarters for the Big Ten Cancer Research Consortium (BTCRC) provided
a clue that Indiana University’s Melvin and Bren Simon Cancer Center
might be a good place to start.
It
was, and since the official kickoff of the initiative was slated for
June 1 during the time of the American Society of Clinical Oncology’s
Annual Meeting in Chicago, I met with Simon Cancer Center Director
Patrick J. Loehrer Sr., MD. He explained that part of the impetus for
the initiative was related to helping save the “endangered species of
assistant professors,” who under current circumstances might have to
wait for years to lead a clinical trial through the cooperative group
mechanism.
“I
remember when I had finished my medical oncology fellowship at Indiana
and was a newly minted medical oncologist eager to get involved in
clinical trials,” he said, adding that he was dismayed by the limited
opportunities.
In
1984, following discussions with Larry Einhorn, MD, and others at
Indiana, Loehrer helped establish the Hoosier Oncology Group, aka, the
HOG, as it is affectionately called by proud citizens of the Hoosier
State, which was modeled to involve more community oncologists in
clinical trials.
He
said there was originally some resistance from oncologists concerned
about losing patients to academic cancer centers, but that the HOG was
designed so patients could be treated the same way in their hometowns.
According
to Loehrer, every HOG study had co-chairs from both the community and
academic centers, and community oncologists were selected to deliver
ASCO presentations.
“These were non-NCI funded trials and community oncologists got involved in the whole process. It
was wonderful,” he said, adding that over subsequent years it became
more difficult to secure industry funding for clinical trials, and that
BTCRC studies will need at least three institutions involved, with one
of the principal investigators being a junior faculty member.
So
when Steven T. Rosen, MD, Director of the Robert H. Lurie Comprehensive
Cancer Center at Northwestern University, suggested in 2011 using the
Big Ten’s athletic conference model to bring cancer centers together,
the idea resonated with Loehrer and other cancer center directors.
Within
a few months the HOG was selected as BTCRC administrative headquarters
and by July 2012, 10 cancer centers were committed to participating in
the consortium (with an 11th joining later), and a steering committee
was formed. Noah Hahn, MD, Associate Professor of Medicine at Indiana
University’s Simon Cancer Center and Chief Medical and Scientific
Officer with HOG, was named interim Executive Officer of the Big Ten
cancer consortium.
HOG,
Loehrer said, will serve strictly in a contract research organization
(CRO) capacity, providing comprehensive study management and support,
and benefits for consortium members including:
- A single, common contract for all institutions;
- A planned streamlined IRB review consolidation;
- Organized clinical trial working groups;
- Sharing specimens with clinically annotated data;
- Development of junior faculty; and
- The opportunity to open trials faster among member institutions.
The venture will also be limited to members of the Big Ten, Loehrer said, and currently includes:
• Indiana University (Indiana University Melvin and Bren Simon Cancer Center);
• Northwestern University (Robert H. Lurie Comprehensive Cancer Center);
• Penn State University (Penn State Hershey Cancer Institute);
• Purdue University (Purdue University Center for Cancer Research;
• Rutgers
University (the Cancer Institute of New Jersey becomes part of Rutgers
on July 1, but Rutgers doesn’t officially join the Big Ten athletic
conference until next year);
• University of Illinois (University of Illinois Cancer Center) ;
• University of Iowa (Holden Comprehensive Cancer Center);
• University of Michigan (University of Michigan Comprehensive Cancer Center);
• University of Minnesota (Masonic Cancer Center);
• University of Nebraska (Fred & Pamela Buffett Cancer Center); and
• University of Wisconsin (Carbone Comprehensive Cancer Center).
When
I first saw the list, Ohio State University’s James Cancer Hospital and
Solove Research Institute seemed conspicuous by its absence. I called
center head Michael A. Caligiuri, MD (a member of OT’s Editorial
Board), who said that OSU had been asked to join, but was “currently
involved in another endeavor that precludes participating at this time.”
He did not disclose the nature of that endeavor.
Cross-referencing
the cancer Big Ten with its athletic counterpart, I also noticed the
absence of Michigan State University’s Breslin Cancer Center, and noted
that the University of Maryland was slated to join the athletic
conference in 2014 at the same time as Rutgers, but its Greenebaum
Cancer Center was not yet on the list.
Loehrer
said that all Big Ten members current and future had been asked to join
the cancer consortium and the 11 institutions listed above had
committed to joining, with each agreeing to pay $14,000 a year over a
proposed three-year period to cover infrastructure costs. He also
acknowledged that this was a work in progress and that more specific
directions would be developed over time.
At
the June 1 kick-off event I spoke with Chandra Belani, MD, who
represents Penn State University’s Hershey Cancer Institute on the BTCRC
steering committee. Belani shared Loehrer’s excitement about the
consortium, and the prospect of developing more early phase trials that
would also help train the next generation of physician-scientists.
He
also talked about the idea of using the Big Ten’s athletic
infrastructure to increase awareness about cancer research and clinical
trials and the potential of raising funds through small contributions by
the thousands of fans attending Big Ten sporting events.
This
model, similar to Stand Up To Cancer’s relationship with Major League
Baseball, may prove an additional avenue to provide outreach and
awareness about cancer research and clinical trials to yet another major
grassroots demographic group.
========================================================
YOU GOT IT RIGHT, YOU PAY $14,000 TO "I DON'T KNOW WHO" AND GET ADMITTED TO THIS CLOSE LEAGUE, WHERE IS THE SUPREME COURT ON THIS! AND WE KNOW WHAT HAPPENED IN TEXAS WITH CPRIT! IF YOU DON'T GET IT, WELL YOU DON'T GET IT!
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