Cancer researcher relocates to lead early drug development at Mays Cancer Center
Mays Cancer Center Annual Report
For Daruka Mahadevan, M.D., Ph.D., several factors contributed to his decision to leave the University of Arizona in Tucson and move his translational drug discovery research and his family to San Antonio, Texas. He appreciates the Mays Cancer Center’s rich history of breadth and depth for early phase drug development through the Institute for Drug Development (IDD).
In August 2019, Ruben Mesa, M.D., FACP, director of the Mays Cancer Center, announced that Dr. Mahadevan was appointed chief of the Division of Hematology and Medical Oncology in the Department of Medicine, effective Dec. 1, 2019. He also is leading patient care services for hematology and medical oncology for the Mays Cancer Center.
“I was excited and intrigued by the history of this place,” he said. “A renowned clinical cancer researcher, Daniel D. Von Hoff, M.D., founded the Institute for Drug Development here. He left San Antonio and went to the University of Arizona, Tucson; Dr. Von Hoff helped develop the concept of personalized therapy for cancer patients. He developed many anticancer drugs that are now routinely used.”
Dr. Von Hoff arrived in San Antonio in 1979 and was named research director of the then-named Cancer Therapy & Research Center (CTRC) in 1988. Under his leadership, the center began its Phase I clinical trials program and the Institute for Drug Development in 1991.
“Dr. Von Hoff left San Antonio in 1999 as a favor to his close friend, Dr. Sydney Salmon, who is another well-known medical oncologist.
Dr. Salmon was dying of pancreatic cancer and asked his friend to take his place as director of the Arizona Cancer Center at the University of Arizona College of Medicine,” said Dr. Mahadevan, noting the irony that Dr. Von Hoff specializes in pancreatic cancer research.
Dr. Mahadevan worked for two years as a hematology oncology fellow under Dr. Von Hoff, who would talk about the center here and its early phase therapeutic development. “Dr. Von Hoff thought this would be a great place to enhance my career. He said I would be a great fit here.”
When Dr. Von Hoff left UA in Tucson, Dr. Mahadevan became the director of the Phase I clinical trials program and also started a drug discovery and development laboratory there. During a 19-year period, he opened and enrolled first-in-human clinical trials for all oncology indications and discovered new drugs to cancer targets in his laboratory. “We have taken drugs designed on the computer all the way to patients.” He was inducted to the National Academy of Inventors as a senior member in 2019.
He said prior experience working for a drug company in England taught him how to clone and humanize mouse antibodies. He was able to bring that knowledge back to the U.S. and use it in his lab to design an antibody for pancreatic cancer. He is concentrating on pancreatic cancer and lymphoma in his recently relocated lab.
Another tie to Dr. Von Hoff resulted in a key research discovery.
“Dr. Von Hoff referred a patient to me — a successful businessman in his early 50s who had been diagnosed with advanced pancreatic cancer. I was able to help him live two more years. During that time, he funded my pancreatic cancer research. We were able to make huge advancements because of his support.
“That patient’s gift allowed us to patent a drug that is an antibody targeting pancreatic cancer,” he said. Dr. Mahadevan created a company, Targeted Cancer Therapeutics, LLC, which out-licensed the drug from the University of Arizona and is now developing the drug.
“The field of pancreatic cancer is a passion of mine. There is no cure, and drugs of the past have shown limited effectiveness,” he said.
Dr. Mahadevan said the antibody he developed can be applied to other cancers, not just pancreatic. However, with his team of two researchers, he said they must concentrate on one type of cancer to be able to make a difference. “If we had more funding, we could look at applying it to other types of cancer.”
The big fields now are immune checkpoint and targeted therapies, he said. “The FDA has approved drugs that can be applied to multiple tumor types. Now, when a patient comes to you with a diagnosis of cancer, you can study the tumor and find a drug that fights that subtype. That is where precision medicine is going. We are learning a lot right now.”
Dr. Mahadevan said while he is excited about early phase drug development being done at the Mays Cancer Center and elsewhere, he tempers his excitement. “We do not have a home run at this time. Tumors are crafty. They will know how to escape our more tailored drugs being developed. They have a plan A, B and C in their systems.
“Our job is to find the multiple resistance mechanisms that tumors have. Once we have done that, we can go after each resistant mechanism. We will be able to anticipate tumor evolution.”
By anticipating the evolution of the cancer’s attack before it happens, Dr. Mahadevan said, “We can make cancer a chronic disease or cure it. This already has happened in breast cancer. Because of the research conducted, breast cancer is now a disease that people survive and live with now.”
His goal for the Mays Cancer Center is to create a portfolio of new drugs that covers all cancer types. For those patients who have exhausted standard of care with FDA approved drugs or are eligible for personalized drugs, this should be where they come to participate in clinical trials of new drugs, he added.
“We are here for patients and their families who want to fight it all the way,” he said. “My mission is to profile every patient at the molecular level. A biopsy of the tumor reveals 600 cancer genes that can be studied. Blood biopsy reveals more than 75 cancer genes. By combining this information, you get the entire genetic picture of the specific cancer that can be targeted.”
He said researchers can also determine germline (inherited) mutations in the blood. “If we can collect this information from each patient, we can create a knowledge base. When the next patient comes in you can see how previous patients did with certain drugs.
“We truly need to understand the underlining pathobiology of each patient’s tumor. You must do it when the tumor is first biopsied or removed. Also, biopsies after progression on a treatment to identify cancer new drug targets is needed. We have to encourage all colleagues to do this.”
Dr. Mahadevan said he is working to recruit clinical researchers who can perform the emerging field of cellular immunotherapy called CAR (chimeric antigen receptor) T-cell therapy. This immunotherapy involves drawing blood from patients and separating out their T cells. Then using an antibody to genetically engineer the T cells and infuse this back into the patient to fight the tumor.
“We do not have this ability now, but we will with the university’s new multi-specialty hospital. I am recruiting people now so we can build a CAR T and a bone marrow transplant program here,” he said. “Cancer continues to beat us but arming ourselves with gene therapy and oncolytic viruses we have new tools beyond traditional surgery, radiation and chemotherapy. We must be revolutionary and fund high-risk projects that have high potential to move the needle. That is critical.”
