TCRF
Funded Research

Immune checkpoint inhibitors had revolutionized cancer treatment. The most versatile such drugs are antibodies that target a receptor molecule called PD-1 or its ligand PD-L1. Although effective in many cancer types, response rates to these drugs rarely exceed 20-30%, necessitating the search for agents that synergize with PD-1/PD-L1 blockers. Using mouse models, we found that the conventional chemotherapeutic drug oxaliplatin has the unique ability to greatly enhance the response to PD-1/PD-L1 blocking antibodies. We will investigate how oxaliplatin increases the effectiveness of PD-1/PD-L1 blockers and will validate these findings in human lung cancer through a Phase I/II clinical study.

Multiple Myeloma is the second most common blood cancer. It arises out of plasma cells, whose normal function is to make antibodies to fight infections. Although in recent years the treatment has become more effective, it remains essentially incurable. One unique aspect of the disease is the close ties to the normal bone marrow cells, specifically the blood vessel cells. Without signals from these cells the cancer dies. We don’t know which signals are the most relevant; our experiments are designed to discover that. This could form the basis for new treatments designed to disrupt these pathways to benefit patients.

Sponsor: John Chute, MD

Cancer cells have many mutations- that is what makes them cancer. Recently it has become clear every cancer patient’s tumor is unique; like snowflakes, cancer cells appear similar from a distance, but when inspected closely no two are exactly the same. This research proposal attempts to better understand how each tumor is different, so that in the future oncologists will be able to pick the right drugs for each unique patient and tumor. Specifically, I am looking to find weaknesses in the cancer cell, so that newer drugs will be able to kill cancer cells while sparing heathy cells.

Sponsor: Trey Ideker, PhD

Immunotherapy is an exciting development in cancer treatment, but has not yet made its mark in sarcoma. The resistance of sarcoma to immunotherapy might be related to the presence of macrophages –a type of immune cell. Here, we aim to understand why sarcomas are full of macrophages, and how macrophages impede the immune system. We will determine how radiation therapy, which is commonly used for patients before surgery, affects these phenomena. Our ultimate goal is to design clinical trials to test drugs targeting macrophages in combination with radiation to make immunotherapy relevant for sarcoma.

Sponsor: Antoni Ribas, MD, PhD

With the help of medical research, the incidences and mortalities of many common cancers (e.g., those from breast, lung and colon cancers) are dropping significantly in US. However, as one of the deadliest malignancies, esophageal carcinoma (EAC) has strikingly risen in incidence (> 600% during the last four decades in USA), with the five-year survival of only 16%. Although Barrett’s esophagus (BE) has long been regarded as a precursor lesion of EAC, no effective preventive strategies is available. Better characterization of EAC pathogenesis and its evolution from BE is greatly needed to decrease the impact of this deadly cancer.

Sponsor: H. Phillip Koeffler, MD, PhD