CPMCRI's Cancer Avatar Project

California Pacific CURRENTS: The online journal of CPMC Research Institute

 

 

CPMCRI is Leading the Future of Cancer Care

In the past 15 years, cancer treatment has significantly improved with the advent of targeted therapies matched to a patient’s specific tumor molecular profile. But these molecular profiles test only certain mutations and not the overall tumor biology, which limits understanding of why patients fail or become resistant to targeted therapies.

Cancer Avatar Project Improves Individualized Cancer Care

To overcome these limitations, scientists at California Pacific Medical Center Research Institute (CPMCRI) are developing a new approach to move beyond the current paradigm for treating cancer.

“Through the Cancer Avatar Project, our cancer scientists are working with CPMC oncologists and surgeons to create cell culture and mouse models, or ‘avatars’, of patients’ tumors, which will give oncologists key information about how well a patient’s tumor might respond to a particular therapy,” says Michael Rowbotham, MD, CPMCRI Scientific Director and Cancer Avatar Project lead.

Live Tumor Samples Provide More Reliable Testing
“Instead of static testing—the traditional cancer research approach—using animal models of human tumor growth provides a more dynamic, accurate picture of how tumors grow, metastasize, and respond to cancer drugs,” says Liliana Soroceanu, PhD, MD, a CPMCRI Senior Scientist who leads the basic science component of the project. “We are creating avatars that replicate the cancerous process in humans and provide a reliable model to test new cancer drugs and treatment combinations, response to treatment, and to better understand how patients become resistant to therapy.”

Samples are being obtained at the time of surgery or biopsy from the tumors of CPMC patients with melanoma and high-grade tumors of the breast, pancreas, colorectum, brain, lung, liver, and ovary. Cells from the tumor are implanted into immunodeficient mice.  Once they grow in mice, tumor cells are harvested to create cell cultures for high-throughput drug testing, used to create more avatars, or stored for later studies.

DNA and RNA samples from the mouse and patient tumor are sequenced to determine the cancer-causing genetic mutations and the genes driving the cancer's growth. The mice are treated with different drugs individually and in combination to determine which treatments shrink tumors, and whether resistance develops. 

“Few medical centers offer something like the Cancer Avatar Project, which will allow us to lead a new paradigm of precision medicine for fully individualized cancer care,” says Mohammed Kashani-Sabet, MD, CPMCRI Senior Scientist and Medical Director of CPMC’s Cancer Programs. “Sutter Health’s three million patients include a diverse cancer population, allowing us to track outcomes from initial diagnosis through long-term follow-up. This is an exciting project that will accelerate our innovation in personalized medicine research in a way that can ultimately improve patient care.”

CPMC Foundation, the philanthropic arm of CPMC, will invest $8.95 million over the next five years in this project and will raise another $10 million for it during the same period. “CPMC is one of only about 20 medical centers worldwide developing cancer avatars for research,” says CPMC Foundation President Doug Nelson. “We thought this was a great investment and would be a compelling opportunity for other philanthropic partners as well.”

CPMCRI's Cancer Avatar Project Team:

Shanaz Dairkee, Ph.D.
Altaf Dar, Ph.D.
David De Semir, Ph.D.
Pierre Desprez, Ph.D.
Mohammed Kashani-Sabet, M.D.
Angela Kim, B.S.
Sean McAllister, Ph.D.
Mehdi Nosrati
Michael Rowbotham, M.D.
Liliana Soroceanu, M.D., Ph.D.
Des Stone
Gregory James Tranah, Ph.D.

The figure below illustrates CPMCRI's approach to using patient-derived xenograft (PDX) models for cancer research:

PDX models are mouse avatars. When transplanted from a human patient with cancer into a mouse, tumors retain the characteristics of the original specimen. PDX models allow researchers to test multiple drugs and drug combinations, to find the one best suited to individual patients.

Learn more about cancer discovery research at CPMCRI.