Because cancer cells mutate, they are able to proliferate, survive, and, in some cases, resist efforts to destroy them. Using genomic and proteomic analyses, computational modeling, and functional testing in sophisticated animal models, Koch Institute investigators are working to uncover the key pathways that allow cancer cells to keep dividing and remain alive. When this "wiring diagram" of cancer cells is complete, it will be possible to develop new strategies to control the disease and combat acquired resistance.
Research Summary The goal in this area is to determine the specific vulnerabilities of cancer cells through systematic analysis of cancer pathways. Cancer cells are fundamentally different from normal cells of the body due to their acquisition of mutations and other alterations in cellular genes. These alterations allow the cancer cells to proliferate abnormally, survive inappropriately, and, in some cases, resist all efforts to destroy them. However, changes in the genomes of cancer cells can also be exploited therapeutically, because the cells develop abnormal dependencies on proteins and pathways that are nonessential in normal cells.
Using a comprehensive combination of genomic and proteomic analyses of cancer, computational modeling of complex cancer pathways, high-throughput chemical and RNAi-based screening, and detailed functional testing in sophisticated animal models of cancer, Koch Institute investigators will elucidate the key pathways that allow cancer cells to keep dividing and remain alive. With this complete "wiring diagram" of cancer cells, we – in collaboration with our industrial partners – will be able to develop new targets for cancer treatment and new strategies to control the disease. Increasingly, this will involve customizing treatments to the particular constellation of mutations present in an individual's cancer.
In-depth analysis of the genetic and biochemical networks that drive tumor development will also allow investigators to anticipate how cancer cells can acquire resistance to specific therapies. Acquired resistance is a major hurdle in cancer treatment today, both with respect to conventional drugs and the new class of molecularly targeted agents. By studying how cancer cells – in the laboratory and in vivo – respond to therapies and how they evolve to resist them, we will be able to develop preemptive measures to block the emergence of resistant clones. As in the case of the successful treatment of HIV, the use of combination therapy to avoid resistance will be critical to achieving durable clinical responses and, increasingly, cures for cancer.
