One Man’s War
Dr. Richard Joseph’s fight to beat aggressive kidney cancers
Richard Joseph, M.D., a Mayo Clinic oncologist and Florida-based researcher, is waging a personal war on kidney cancer. And he is fighting on multiple fronts – trying to conquer the disease with two of the most promising new weapons in the anti-cancer arsenal.
In one suite of studies, Dr. Joseph is searching for just a few genetic variants in the genomes of clear cell kidney cancers from among the millions of changes that make a person unique. Armed with this information, Dr. Joseph believes he can begin tailoring treatment to individual patients and their tumors, rather than lumping all clear cell renal cell carcinoma patients together. This type of tailored or personalized medicine is at the core of what Mayo Clinic is working to achieve through scores of studies active within its Center for Individualized Medicine.
“Certain drugs might work for a small minority, but there is no way of knowing who will clearly benefit. It is necessary to identify patients who are going to be helped by the drugs they are given,” says Dr. Joseph. “Angiogenesis and immune evasion are known pathways that contribute to the metastatic process in kidney cancer and inhibition of angiogenesis and reversing immune evasion benefit a subset of patients with kidney cancer. Unfortunately, we do not have molecular markers that will predict benefit from a specific therapy.”
In a second set of medical investigations, Dr. Joseph is trying to train the body’s own immune system to seek out and eliminate clear cell renal cell carcinomas in much the same way the body fights off a seasonal flu. This field of research is known as cancer immunology. Already, research in this area has led to several new chemotherapies that gravitate toward tumors based on chemical flags called antigens. It’s the same chemical process that helps the body identify viruses and bacterial infections while ignoring the surrounding healthy human cells. Many such studies are under way in Mayo’s Department of Molecular Medicine.
To accomplish these studies, Dr. Joseph recently received two grants totaling more than $400,000 – one from the American Association for Cancer Research via its 2012 Judah Folkman Career Development Award for Antiangiogenesis Research, the second from the Gerstner Family Career Development Award, issued by Mayo’s Center for Individualized Medicine.
At the advent of his career
Dr. Joseph is an oncologist and translational researcher, who has one foot in the lab bench and another grounded at the patient’s bedside.
As a fellow at M.D. Anderson, Dr. Joseph focused on immune therapies and the most immunogenic tumors, melanoma and kidney cancer. As a junior faculty member at Mayo Clinic Florida, he is now focusing his research on kidney cancer in large part because of his mentor, Alexander Parker, Ph.D., a nationally known expert in kidney cancer research and associate director of the Center for Individualized Medicine.
Dr. Parker has created a renal registry in Mayo’s Biospecimens and Accessioning Processing Lab that allows researchers to analyze well-preserved tissues and compare results with clinical data from the patient’s medical record. He is leveraging this renal registry because he believes the tools of individualized medicine will usher in a new generation of therapies for kidney cancer.
A key step in providing individualized therapies to kidney cancer patients is to systematically evaluate the genetic pathways that give rise to clear cell renal cell carcinomas. After identification of alternate pathways, the researchers want to test whether blocking these pathways – one at a time – can help stop tumor growth.
Stopping tumors in their tracks
Already, Dr. Joseph’s preliminary work has identified two potential subtypes of clear cell renal cell carcinoma – angiogenic and immune evasive. Through the American Association for Cancer Research grant, Dr. Joseph will utilize Mayo’s expertise in validating these subtypes in a larger group of patient samples.
The work associated with his Gerstner Grant includes targeting, evaluating and inhibiting this pathway in kidney cancer, finding the markers that are associated with a response. The research builds on his team’s observation that the insulin-like growth factor pathway is activated in about half of all patients with clear cell renal cell carcinoma. Activation of this pathway is also marked with a remarkably poor prognosis.
Dr. Joseph wants to hone in on this insulin pathway in kidney cancers and use this knowledge to launch the first individualized trial in clear cell renal cell carcinoma. The team will be sequencing multiple tumors, and Mayo’s Biospecimen lab will help with extraction of RNA before sequencing.
“I believe that improving care for patients with kidney cancer is going to be incremental, and one of the necessary steps is to identify and target specific attributes and pathways within the individual patient,” says Dr. Joseph. “We don’t want to treat everybody the same.”