Rom David Keshet, MD, PhD
Project Title
Sensitizing immunotherapy for inhibiting colon cancer progression to the liver by blocking tumor-associated LDL
About the Investigator
I earned my MD degree in Tel-Aviv University and specialized in internal medicine at the Tel-Aviv Sourasky medical center. I studied cancer metabolism during my PhD and my post-doctoral fellowship at the Weizmann Institute of Science. In 2018, I have joined the Bert W. Strassburger Metabolic Center for Preventive Medicine at the Sheba Medical Center as physician-scientist. To upgrade my cancer research capabilities, during 2023 I joined the lab of Prof. Robert Weinberg at MIT, USA to work as a visiting scientist. My research lab reveals the roles of lipoproteins (the lipid-carrying particles in our blood) in the diagnosis and treatment of cancer.
About the Research
Colon cancer is one of the most common cancers worldwide, and for many patients the disease spreads to the liver. When this happens, treatment options become extremely limited and survival rates drop sharply—despite major advances in cancer medicine. One of the biggest mysteries is why immunotherapies, which can be life-saving in other cancers, usually fail once colon cancer reaches the liver. Our research addresses this mystery by uncovering a completely new way cancer may hide from the immune system. Instead of focusing only on substances released directly by tumors, we discovered that cancer can “reprogram” particles that already exist in the body—specifically, LDL cholesterol, often known as “bad cholesterol.” In cancer patients, this cholesterol is altered into a new form we call tumor-associated LDL, that actively weakens immune defenses and prepares the liver to accept cancer cells even before they arrive. We found that tumor-associated LDL pushes immune cells to support cancer growth instead of fighting it. In animal models, exposure to this altered particle caused liver changes that closely resemble early metastatic disease.
Our goal is to fully understand how this process works and, most importantly, how to stop it. We aim to block cancer’s ability to use altered LDL as a shield and combine this strategy with existing immunotherapies. If successful, this approach could dramatically improve the effectiveness of immunotherapy for patients with liver metastases. This work opens the door to a new way of thinking about cancer treatment—by targeting the body’s own modified molecules—and has the potential to benefit not only colon cancer patients, but many others in the future.
