"With cancer, things change too rapidly for doctors to be able to rely on yesterday’s guidelines for long."
- Vincent T. DeVita, Jr, MD The Death of Cancer
The treatment of cancer is evolving. While we once relied on drugs aimed at fast growing cells, we are now developing new therapies to target specific growth pathways and immune system components shown to be important in cancer cell growth, survival and migration to distant locations. Genetic assessment of tumor tissue can provide insight into which therapies or drugs might be the most successful against a particular cancer.
Harnessing Molecular Genomics
Tumor genetic testing involves taking a piece of tumor (or blood or bone marrow in cancers such as leukemia or multiple myeloma) and reverse-engineering it to understand what went wrong in the cells to make them grow so rapidly. Genetics cannot tell the full story on this – far from it – but it can give us clues as to what types of growth pathways are activated. With our current technology, we can get a molecular fingerprint of the tumor. We then look for oncogenes or tumor suppressor genes. An oncogene is a gene that, when turned on by a mutation in that gene, increases cell growth (e.g. EGFR, KRAS, etc.), like hitting the gas pedal in your car. A tumor suppressor gene is a gene that, when turned off by a mutation or other change, increases growth in a cell (e.g. TP53 or RB). Tumor suppressor inactivating mutations are like cutting the brakes on a car so that it cannot stop.
Tumor genetic testing can look for a select number of mutations (most commonly up to a few hundred) or even sequence the whole tumor. What we look for are mutations in oncogenes or tumor suppressor genes that we can target with treatments to block growth pathways turned on by these mutations.
Clinical Activation at Moffitt
At Moffitt Cancer Center, the Personalized Medicine Clinical Service (PMCS) was developed to help interpret tumor genetic alterations and identify treatment options that may be helpful for patients, either now or in the future. Since its inception in early 2014, the PMCS meets weekly to review all tumor genetic sequencing results for any Moffitt patient for whom genetic tumor testing is performed. Difficult cases that require the insight of an expanded multidisciplinary group may be referred to the Clinical Genomic Action Committee (CGAC), which serves as Moffitt Cancer Center’s Molecular Tumor Board. The CGAC consists of numerous experts across disciplines including oncologists, pathologists, basic scientists, clinical geneticists, nurses, pharmacists and bio- informaticists. Dr. Christine Walko chairs the CGAC committee and works closely with the clinical teams.
The goal of the PMCS and CGAC is to identify and discuss treatment options that may be helpful, and to ultimately communicate this to the medical team. These treatment options may include already approved drugs being used in other cancer types and/or clinical trials. Molecular targeted cancer therapy is a fast-growing field of inquiry. Numerous clinical trials are being developed – some of which are currently enrolling patients with different tumor types that all have the same genetic mutations. These are called “basket trials.” Patients with a certain genetic mutation can be assigned to a “basket” of patients with the same mutation despite different cancer diagnoses. They will all receive the same drug targeted to that specific mutation. Trials like these include the NCI MATCH trial with more than 20 different arms (or “baskets”) for specific genetic mutations and matched therapies. While some of these trials may not be the best fit for patients with tumors that are hard to biopsy (like some brain tumors), the trial results will hopefully provide more genetic-guided treatment options for patients of a variety of tumor types.
If you missed Dr. Walko's talk at the Florida Society of Clinical Oncology (FLASCO) Genomics Grand Rounds, "Going Beyond The Standard Of Care: Translation Of Personalized Medicine Into The Clinical Oncology Setting," learn even more about tumor genome profiling and the CGAC by viewing the presentation here.