Decoding Cancer: New Program Uses Genetics to Target Cancer 

Stanford's Cancer Genetics Program was developed with two goals in mind: first, to identify novel drug therapies for cancer patients with advanced disease; and then to systematically catalogue data from every patient to improve understanding of the genetic characteristics of cancer, and continually refine the ability to treat it.

"We have established an integrated genetically-driven process for cancer patients who haven't responded well to standard treatment and need to explore alternative strategies," said James Ford, MD, director of the Cancer Genetics Program.

Cancer is a disease of genetic malfunction and mutation. Since mutations are what make the cells abnormal, scientists try to use these mutations as targets for anti-cancer drugs. Researchers search for (and also create) chemical compounds that selectively bind to specific gene mutations in order to disable or kill cells. Such "targeted therapies" offer the possibility to eliminate cancer cells using greater precision and causing fewer side effects than more toxic treatments like radiation and chemotherapy.

Genetic-based cancer treatment is a rapidly evolving area of medicine. Many molecular-targeting drugs are being explored at research centers and developed by industry. SCI's program provides a framework in which experts in genetics, oncology and cancer biology jointly examine the molecular profiles of hard-to-treat tumors. Based on the mutations identified, the team suggests treatment options, including clinical trials patients may qualify for, or an "off label" use of a cancer drug.

"One goal is to identify a molecular alteration that allows for a targeted treatment that we might not otherwise have thought of for that particular patient," said Ford, an associate professor of oncology and genetics.

STAMP-ing out cancer

To that end, the Cancer Genetics Program has developed its own detailed genomic test to identify the best available drugs to treat each patient's tumor, regardless of its location. Cancer Genetics Program members, including professor of pathology and hematology, James Zehnder, MD, worked for over a year to refine Stanford's analytic tool, called STAMP (Solid Tumor Actionable Mutation Panel), which provides highly sensitive and accurate examination of approximately 200 different genes implicated in cancer.

"The amount of work we did to make sure that this assay is completely validated gives us confidence in its accuracy," said SCI member Ash Alizadeh, MD, PhD, an assistant professor of oncology with expertise in genetics and computational biology.

Using their own test gives program members many advantages, including reduced cost and increased convenience. Customization is also enhanced when the "end users" of the data build their own screening tools.

"Because this test was developed in-house, we have the flexibility to modify the testing to focus on areas most relevant to patient treatment decisions and clinical trial enrollment, and quickly respond to new discoveries," said SCI member Zehnder, a leader in applying next generation genetic sequencing to the understanding and treatment of cancer and other immune-related conditions.

The heart of the Cancer Genetics Program is its Molecular Tumor Board, where every two weeks specialists gather to examine the precise genomic data as well as the subtle nuances of each patient's difficult cancer case. Age, gender, family history and previous treatments are all part of the conversation, as is the potential impact of rigorous treatment and side effects on current health status and quality of life.

"Every patient we see is different, so searching for the best outcome for each requires examining massive amounts of data," said Ford. "Christina Curtis and others are important to the team, because they are particularly skilled at taking huge data sets and asking individual patient questions as well as broad 'population-type' questions."

SCI member Christina Curtis, PhD, is an associate professor of oncology and genetics, recently recruited from the University of Southern California for her expertise in molecular and computational biology, and her highly collaborative approach to cancer research.

"Our application of state-of-the-art genomic technologies and computational approaches enable the dynamic monitoring of treatment response on a patient-by- patient level," said Curtis. "We also aim to integrate this clinical data with population-level data to refine our understanding of disease biology and mechanisms of resistance to improve the diagnosis and treatment of future cancer patients."

The program also records how many patients have mutations that are treatable with targeted therapy, how often patients receive a recommended drug and what are some of the roadblocks to getting patients targeted treatments. All of these factors provide valuable data to understand how genetically targeted therapies can benefit many more patients in the future.

Use of genetic sequencing can also uncover cancer-associated mutations that are inherited, meaning that the patient's family members and offspring have increased cancer risk. For this reason, the program and tumor board include genetic counselors who educate about familial cancer, provide clear options for medical or surgical interventions and enhance the quality of life for high-risk cancer families.

Reprinted in part with permission from the Stanford Cancer Institute News. For the full story, go to stanford.cancer.edu.