Damon Runyon News

Age is the greatest risk factor for developing cancer due to the continuous and life-long accumulation of DNA mutations. Although we have identified causes of childhood cancer, including the inheritance of cancer-predisposing genes, other major contributing factors have not yet been identified. Blood cancer is the most common cancer in children and sequencing data indicate that the first genetic mutations occur during fetal development. Dr.

Sex differences are markedly evident in many types of cancer, and one of the major contributors to sex-biased differences lies in the sex chromosomes. In contrast to the traditional view that Y chromosome-encoded proteins only function in male reproductive organs, recent evidence suggests that select Y chromosome-encoded proteins are also expressed in male non-reproductive tissues. Furthermore, dysregulation of the Y chromosome-encoded proteins has been implicated in cancers in non-reproductive organs.

Genetically engineered immune cell therapies have emerged as breakthroughs in the treatment of certain blood cancers. However, these advances have been limited to the minority of cancers that express a cell surface protein on all tumor cells; this protein is absent from essential normal tissues and can be recognized and targeted by therapeutic immune cells. Dr. Jan seeks to develop synthetic biology tools to engineer immune cells to recognize the heterogeneous tumor proteins present on many advanced cancers and then activate the body's tumor clearance mechanisms.

Many cancer diagnostic and treatment strategies use markers on the cell surface to find and kill cancer cells in a sea of healthy tissue. Dr. Flynn's research aims to expand our knowledge of what molecules are found on the surface of cancer cells. He will focus on acute myeloid leukemia (AML), as there is a major unmet clinical need for new curative treatments. Specifically, he aims to define RNA as a new cell surface molecule that could have unique structures on AML cells. With this knowledge he will develop antibodies to selectively detect cancer cells and enable tumor killing.

About 70% of pediatric leukemias and 10% of adult leukemias are caused by a genetic disruption in which the mixed lineage leukemia (MLL) 1 gene breaks off and attaches to a different chromosome. This event, known as a chromosomal translocation, gives rise to a distinct subset of leukemias called MLL-rearranged acute myeloid and lymphoblastic leukemias (AML or ALL). Novel treatments for these cancers represent a major unmet medical need.

Up to 50% of patients with acute myeloid leukemia (AML) have a genetic alteration called DNA methylation, in which a carbon methyl group is added to the DNA molecule, typically turning the methylated gene "off." A mainstay of therapy is the use of hypomethylating agents, which prevent copying of these modifications during cell division, but this therapy is effective in only 20-30% of patients. Using chemical and genetic manipulation in mouse bone marrow, Dr.

The microorganisms that live in the digestive tract, also known as the intestinal microbiome, have emerged as important factors in patients' response to cancer therapy. Studies have found that the intestinal microbiome can modulate the anti-tumor immune response to several types of therapy, including chimeric antigen receptor T cell (CAR T cell) therapy, in which a patient's own immune cells are genetically modified to target their cancer. CAR T therapy has led to unprecedented responses in patients with high-risk blood cancers such as leukemia and lymphoma.

Chimeric antigen receptor T cell (CAR T cell) therapy, in which a patient's own immune cells are engineered to target their cancer, has changed the treatment landscape for many blood cancers. Despite promising early results, however, long-term follow-up has revealed that nearly half of patients treated with CAR T cells eventually experience cancer recurrence. Using a variety of techniques in cell lines and patient samples, Dr.

Mutations in the EGFR gene were identified as the first targetable mutations in lung cancer about two decades ago. Since then, multiple targeted therapies have been approved and prolonged many lives. However, about 15% of EGFR mutations are atypical and do not have a current approved targeted therapy. Dr. Le is leading multiple clinical trials to address this unmet need. With new treatments potentially entering the clinic, new mechanisms of treatment resistance will likely evolve. Dr.

Pancreatic cancer develops in the midst of intense scarring and fibrous connective tissue (fibrosis). The architects of this scarring are cells called fibroblasts, known to fuel cancer growth and promote treatment resistance. Dr. Delitto's research is focused on the interface between cancer-induced fibrosis and the immune system. He has shown that fibroblasts play a significant role in shielding cancer cells from immune cells. By altering how fibroblasts sense tissue damage, Dr. Delitto has uncovered a mechanism that reactivates the immune system to fight the tumor.