Building a Precision Medicine Team

“Doctors have always recognized that every patient is unique, and doctors have always tried to tailor their treatments as best they can to individuals. You can match a blood transfusion to a blood type — that was an important discovery. What if matching a cancer cure to our genetic code was just as easy, just as standard? What if figuring out the right dose of medicine was as simple as taking our temperature?”

President Obama
State of the Union Address, Precision Medicine Initiative
January 30, 2015

A thought leader and always ahead of the curve, Santosh Kesari, MD, PhD, was putting precision medicine into practice for treating brain tumors long before Joe Biden’s Moonshot Initiative.

Dr. Kesari is professor of neurosciences at Saint John’s Cancer Institute and chair of the department of translational neuro-oncology and neurotherapeutics at Pacific Neuroscience Institute (PNI). He says, “In fact, we have been using our trademarked tagline for many years believing that this is the future of cancer care – Personalized Care in the Era of Personalized Medicine^TM.

Illustrating this philosophy of elegant targeted science, a recent study published in Science Translational Medicine has shown great promise in the clinical setting almost doubling the life expectancy of glioblastoma multiforme (GBM) patients in a small clinical trial. Based on his doctoral work and six years of research on viral gene delivery, Dr. Kesari’s thesis explores the idea of cascading systems. In a two-step process, a manipulated virus is introduced into brain tumor cells and induces it to make an enzyme which acts as a “cell detonator.” In the second step of the treatment cascade, a prodrug that is inactive by itself is added. When it comes into contact with the enzyme inside the tumor cell it is activated, transforms into a toxic drug and kills the cancer cell.

Called oncolytic virotherapy, the use of this kind of virus-drug combo has led to the development of new clinical trials to be conducted through Saint John’s Cancer Institute, some of which will include direct intra-tumoral injections. Patients around the country have already benefited from this therapy.

Over the past year, Dr. Kesari has built up his team at PNI to push forward research efforts on multiple fronts ranging from basic science to translational research programs. The goal of the Precision Medicine Program at PNI is to move potential therapy candidates into clinical trials and then into the clinic to treat patients. And in collaboration with Dr. Dave S. Hoon, founding director of the department of molecular oncology at Saint John’s Cancer Institute, patient samples can be sequenced and characterized to further personalize treatment.

Ivan Babic, PhD, was recently appointed as assistant professor of translational neuro-oncology and neurotherapeutics at Saint John’s Cancer Institute. Dr. Babic’s research work focuses on targeted therapies based on cancer cell metabolism and molecular characteristics.

Venkata Yenugonda, PhD, joined the Saint John’s Cancer Institute as an Associate Professor in the department of translational neuro-oncology and neurotherapeutics. His aim is to advance ongoing translational neuro-oncological drug discovery projects and for over a decade Dr. Yenugonda’s research has focused on discovery and development of novel small molecule inhibitors in the fields of cancer and neuroscience. “Despite advances in brain cancer research, overall patient survival remains poor. The existence of the blood–brain barrier (BBB) restricts the delivery of therapeutic molecules into the brain. Therefore, enhancement of the permeability of the BBB and being able to transport these small molecule drugs across appears to be a promising strategy to improve drug absorption and treatment efficacy.” Recent work in Europe and Canada confirms this idea.

Elmar Nurmemmadov, PhD, an assistant professor of translational neuro-oncology and neurotherapeutics with the Institute, is an expert in the field of cancer drug discovery. He works with Dr. Kesari on the discovery of therapeutic agents for cancer, particularly the brain cancer glioblastoma. “The need for new cancer drugs to address specific molecular targets is significant,” he says. “We are focusing our efforts on targeting regulatory proteins that play key roles in the genesis as well as progression of cancer. My role spans from early discovery of such promising therapeutics to their preclinical validation.” Dr. Nurmemmadov, who recently obtained his MBA focusing on innovation and entrepreneurship says, “The therapeutic research angle at the Saint John’s Cancer Institute provides the flexibility to do leading-edge research and then translate the findings into clinical practice. This is a unique place where the combination of innovative research and strong leadership can result in novel biomedical therapies.”

Natsuko Nomura manages the team’s science research portfolio and focuses her research efforts on basic science and translational research uncovering pathways and mechanisms which contribute to the development of brain cancer.

Marlon Saria, PhD, RN, a long time advanced practice nurse researcher, recently earned his doctorate and heads up the team’s clinical outcomes research efforts. Research and clinical trials go hand in hand and patients who are receiving treatment for their disease still need a support structure. Dr. Saria says, “A significant part of our work is to identify needs and provide support to patients and their families as they navigate the cancer experience. The landscape of cancer treatment is changing before our very eyes. Drugs are more precise, side effects are fewer and milder, and patients are living longer. Yet there is still much to be done.”

With more research opportunities in the works, Dr. Kesari continues to expand his team. For more information about PNI’s Precision Medicine Program, please contact us at neuro.oncology@jwci.org or 310-829-8265.