Genomics leads cancer discoveries in new directions
"Dr. Gandara and his expertise saved my life."
Elizabeth Lacasia is not one to shy away when something comes out of left field. When the active, nonsmoker was diagnosed eight years ago with a rare form of lung cancer – bronchioalveolar carcinoma – she underwent a difficult course of conventional treatment including two surgeries and a combination of chemotherapies. When her cancer continued to spread, her oncologist advised her to look into palliative care. But Lacasia, who married two years prior to her diagnosis, wasn’t ready to give up.
Because of her background in biotech, Lacasia knew that lung cancer was a complex disease with potentially more effective treatment options than through the standard of care approach.
"I asked a specialist for the names of thoracic oncologists who had experience treating my cancer sub-type and Dr. Gandarawas on the list," she recalls. "I had a positive opinion of UC Davis as my husband and a number of our friends graduated from there. So, we decided to meet with Dr. Gandara."
It was a fortuitous choice. David Gandara, professor of internal medicine and director of the UC Davis Comprehensive Cancer Center’s thoracic oncology program, does groundbreaking research and provides clinical care in the field of personalized treatment for cancer, using information available through genetic testing of each patient’s tumor to find the most effective therapies. Gandara put a sample of Lacasia’s tumor through a battery of molecular and genetic tests to help identify which drugs might best combat it.
Based on the findings, he suggested a clinical trial with a novel treatment approach aimed at Lacasia’s specific type of cancer.The treatment proved to be extraordinarily effective, resulting in a complete response with no current evidence of cancer.
"Genomics testing allows us to personalize cancer treatment in ways that were not thought possible only a decade ago," says Gandara, who was honored last year with the Scientific Award from the International Association for the Study of Lung Cancer. "It is changing the paradigm of cancer therapy."
Gandara is one of many researchers and clinicians at the UC Davis Comprehensive Cancer Center taking the battle against cancer to an important new front – the fast-moving field of cancer genomics. It involves not only mapping DNA sequences but also better understanding the effects of mutations. The lightning-speed development of technology as well as information processing have made the field a gold mine for learning about disease processes and finding new treatment targets.
Basic research underlies advances
The UC Davis Comprehensive Cancer Center achieved its National Cancer Institute comprehensive designation in 2012 to great acclaim and justified pride in accomplishment. One of only 41 such centers in the nation, the designation recognizes the institution as a top-notch research center that is also on the leading edge of clinical care delivery.
"Our commitment is stronger than ever to comprehensively move the science forward to benefit our patients and break barriers to beat cancer," said Ralph de Vere White, center director. "Our genomics research is taking advantage of the incredible advances in technology and new biological systems to discover how cancers at the most fundamental level are susceptible to treatment."
Genomics testing allows us to personalize cancer treatment in ways that were not thought possible only a decade ago. It is changing the paradigm of cancer therapy.
Luis Carvajal-Carmona, assistant professor of biochemistry and molecular medicine, for example, is looking at the smallest genetic differences between individuals – in single nucleotide polymorphisms, called SNPs ("snips"). DNA is constructed from sequences of four base nucleotides, abbreviated as A, T, C and G. While most of a population’s genetic code is pretty similar, an individual may have, for example, a "T" in one position while others have a "G," the result of a genetic mutation. Using a variety of high-throughput genetic analysis techniques, Carvajal-Carmona is searching for SNPs in remote villages high in the mountains in Colombia, where some families have particularly high incidences of breast and colon cancer. According to Carvajal-Carmona, because of centuries of isolation, the populations there are otherwise so homogenous that genetic mutations are relatively rare and more likely to yield significant findings.
"We are optimistic that this work can rapidly contribute to better personalized medicine and global cancer health," says Carvajal-Carmona. "We hope that our studies will benefit the people from these remote regions, and also contribute to improving cancer prevention and treatment for people all over the world."
The research laboratory of David Segal, associate professor of biochemistry and molecular medicine, is looking at SNPs in another way – to unlock clues to how cancers develop. Funded by the W. M. Keck Foundation, Segal’s team of researchers is using genome engineering techniques to introduce specific SNPs into stem cells to find out their molecular effects.
"Our research is trying to understand the mechanisms by which DNA changes increase the risk of cancer," Segal said. "If we can understand the pathways leading to disease, then maybe we can discover specific targets for therapeutic interventions."
One promising avenue is gene therapy for neurofibromatosis, a genetic disease that carries a high risk of tumor formation. Children with the syndrome often develop multiple neurofibromas – tumors of the nerve sheath – that can result in physical disfigurement, pain and cognitive disabilities. Segal’s lab is engineering transcription factors – proteins that bind to specific DNA sequences, thereby controlling the flow of genetic information – that very specifically home in on the neurofibromas and disrupt their growth.
A home for discovery ... and healing
The Comprehensive Cancer Center recently completed a 46,000-square-foot addition to the existing 63,000 square-foot facility. The expanded clinical and research facilities were made possible by a capital and endowment initiative that received many large and small gifts from community members, many of whom feel a deep connection to the cancer center because of family members who received care there.
The enlarged space means that cancer clinical care teams previously located in various buildings are now onsite. In addition, research and clinical care take place together, promoting collaboration among cancer center staff, faculty and researchers, especially in clinical trials.
"We now have a seamless transition between patients, laboratories and early-phase clinical trials," says de Vere White. "This facilitates discoveries that can quickly be applied to new treatments for our patients."
As the Comprehensive Cancer Center looks enthusiastically to the future, so does Lacasia.
More than four years since she began the clinical trial that turned her disease around, she and Gandara are planning the next steps in her treatment plan. A more comprehensive genomic assessment of her original tissue samples is in the works, as the test panels have broadened and improved since her earlier tests. According to Gandara, this may provide essential information for new avenues of therapy should her cancer recur.
In the meantime, Lacasia is enjoying her life, hiking and traveling with her husband, a gift she credits to taking part in the advances in genomics research.
"Dr. Gandara and his expertise saved my life."