 a target for new therapeutic intervention? “Telomerase has not been a major focus of anti-cancer drug development,” says Garraway, “but perhaps we should re-evaluate the premise empirically in cancers with mutations affecting telomerase.” In general, discovering links between regulatory elements and cancer risk promises to generate many new leads for researchers to follow in the coming years.
Full Speed Ahead
When targeted therapies were first introduced, the approval process for each took years. Now an existing drug can gain approval for a new cancer with a specific mutation relatively quickly. However, it often takes a national effort to identify enough patients with rare mutations to perform clinical trials properly. That difficulty motivated 15 institutions to form the Lung Cancer Mutation Consortium three years ago, with Bruce Johnson, MD (DFCI) as a co-principal investigator.
“The new paradigm in clinical trails is a genotype-specific and cancer-non-specific trial,” says David Kwiatkowski, who is planning such a trial to test an existing drug, the mTOR inhibitor everolimus, in cancers with mutations in either of two genes (TSC1 and 2) that regulate mTOR, a master kinase. Kwiatkowski first discovered one of these genes as the cause of an inherited cancer syndrome, Tuberous Sclerosis Complex, and the mutations have been identified in bladder cancer, a type of sarcoma, and pancreatic neuroendocrine tumors. Now the Cancer Genome Atlas (TCGA) project (Matthew Meyerson, MD, PhD (DFCI), co-principal investigator) has discovered low frequencies of these mutations in many types of cancer. Kwiatkowski wants to see if everolimus can be repurposed for treating patients with any cancer that has mutations in TSC1 or TSC2.
Like Moore’s law in electronics, technological innovations are helping cancer genetics research progress exponentially. Thanks in part to DF/HCC’s involvement in large collaborations like the Lung Cancer Mutation Consortium and TGCA, its discoveries are being rapidly translated into the clinic.
Research detailed in this article was funded in part by NIH grants, including CA065164, CA12700, CA120060, CA137008, CA141457-01, CA090578, CA140594, CA122794, CA163896, HG006097-01, CA148537, CA131341, CA148065, CA009172, GM07753, OD002750, CA126674, CA120964, NS031535, AR055619-06, and CA154923-02.
— Cathryn Delude