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P11409 Remember it is a about the Cure not the Coin.
Myself I have had 4 Family Members passed away from Prostate Cancer.
This trial looked at dasatinib and chemotherapy for prostate cancer that has spread to other parts of the body and is no longer responding to hormone therapy.
Prostate cancer that is no longer responding to
hormone therapy is known as hormone refractory prostate cancer. Doctors may use
chemotherapy to treat it. The drug they most often use is called
docetaxel (Taxotere). You have steroids with docetaxel to reduce the risk of side effects.
Dasatinib (Sprycel) is a type of
biological therapy called a
cancer growth blocker. It stops signals that cancer cells use to divide and grow. Researchers hoped it would be useful for men who have hormone refractory prostate cancer.
In this trial, half the men had docetaxel and dasatinib, and half had docetaxel and a dummy drug (
placebo).
The aims of the trial were to
- Find out if dasatinib with docetaxel works better than docetaxel alone for hormone refractory prostate cancer
- Learn more about the side effects
From Below.
Disease Type: Cancer
Projects 11400 and 11401 examine Abl1 and Src kinases.
Abl kinase has a special place in the history of cancer therapeutics,
‘dispelling the long-held myth that it was not feasible to develop selective inhibitors of key cell-signaling molecules as safe and effective medicines.’ Novartis’ development of the drug imatinib (or Gleevec commercially) to treat chronic myelogenous leukemia (CML) specifically targets a mutant Abl kinase that results from a chromosomal abnormality called ‘the Philadelphia chromosome’. There is even a book out recently that chronicles the development of Gleevec (
The Philadelphia Chromosome).
While the success of imatinib was remarkable, many patients develop resistance to it and regress. A more recent drug targeting Abl kinase, ponatinib of Ariad Pharmaceuticals (Iclusig commercially), has been developed
that overcomes some of these resistance mutations. However, now even ponatinib has been found to be susceptible to resistance mutants. With these simulations of Abl kinase, we are hoping to begin to understand a structural basis for the development of resistance mutants so we can develop drugs that anticipate and overcome them before the patient even has to experience regression. But to do this we will need many long timescale trajectories of Abl and later its mutants to achieve this deeper understanding of the development of resistance in CML. Additionally, this knowledge could inform models of resistance development in other cancers that result from kinase mutations or kinase up-regulation.
The Src gene was first discovered as responsible for the tumorogenicity of Rous sarcoma virus. This gene is also present in animals, and it is in fact a mutated Src gene that is injected back into the host that causes cancer, not a viral gene. The discovery that cancer was a result of mutated naturally occuring genes and not viral ones was a milestone in cancer research and Harold E. Varmus and J. Michael Bishop were awarded
the Nobel Prize in Physiology or Medicine for this and related discoveries of the cellular origin of retroviral oncogenes in 1989.
Since then Src has been found to be over-expressed and/or highly activated in a variety of cancers, most notably linked to metastasis in breast, prostate, and colon cancers. The drug dasatinib of Bristol-Myers Squibb (Sprycel commercially), has been approved for treatment of CML (described more fully in our blog post on
Abl kinase), but it was also
recently in clinical trials for metastatic prostate cancer due to its affinity for Src kinase.
This project is managed by Dr. Sonya Hanson at Memorial Sloan Kettering Cancer Center.
http://www.choderalab.org/members/#sonya-hansonSonya Hanson is a postdoctoral fellow at the Memorial Sloan Kettering Cancer Center studying the origin of selectivity of target small molecule kinase inhibitors for the treatment of various cancers.
post edited by bcavnaugh - 2017/10/22 09:31:51