Damon Runyon News

Myelodysplastic syndromes (MDS) are a heterogeneous group of blood disorders characterized by abnormal maturation of the hematopoietic blood cells and premature death of these immature cells leading ultimately to bone marrow failure. Patients with MDS are also at increased risk of developing acute myelogenous and acute lymphoblastic leukemias. Currently available treatments for MDS include serial blood transfusions for refractory anemia, hematopoietic cell growth hormone therapy, and eventually chemotherapy and bone marrow transplantation.

Bone marrow transplant (BMT) is a treatment approach where cells from a healthy donor are given to a patient with blood cancer who has not responded to other treatments. Unfortunately, there are risks to this procedure such as graft-versus-host disease (GVHD), which occurs if the cells from the donor attack the "foreign" patient tissue; this can cause serious organ damage and is life-threatening. Melody is investigating an approach to decrease GVHD while also maintaining the benefits of BMT, specifically graft versus tumor (GVT).

Christopher’s research centers on the earliest steps whereby normal cells transform into abnormal cells with the potential to become cancer. He will focus on better understanding the first steps of the process by which normal blood cells become lymphomas, cancers that are generally thought to arise from blood cells that have already committed to becoming lymphocytes, an important component of the immune system. He hypothesizes, however, that some lymphomas actually arise from earlier hematopoietic stem cells (HSCs).

The development of HER2-targeted therapies over the past two decades has had tremendous positive impact on the lives of HER2-positive breast cancer patients. However, tumor resistance to these therapies remains a significant challenge: a sizable portion of patients with early-stage HER2-positive breast cancer develop recurrence, and the vast majority of patients with metastatic HER2-positive breast cancer eventually progress through treatment.

Dr. Bhabha is focusing on understanding the function of structures on the cell surface called cilia, which play important roles in signaling, sensing the cell’s environment, and regulating cell growth. One particular signaling pathway in cilia, Hedgehog, has been shown to be dysregulated in multiple cancers, including basal cell carcinoma, medulloblastoma, and pancreatic cancer. She aims to characterize the structure and dynamics of the large, multi-protein complexes that function within the cilia.

Cancer cells frequently rewire intracellular metabolic pathways in order to support rapid proliferation. In addition to serving as building blocks for cell growth, metabolites also serve as critical substrates for enzymes that control gene expression programs. Changes in intracellular metabolites can therefore have a profound effect on cellular functions including survival, growth and differentiation. As the Jack Sorrell Fellow of the Damon Runyon Cancer Research Foundation, Dr. Finley found that specific intracellular metabolites promote the self-renewal of embryonic stem cells.

Genes that are mutated, amplified, or altered in cancer contribute directly to tumor development, maintenance, and metastasis. The Ras-MAPK signaling pathway contains two of the most frequently altered genes across all cancers. Ras-MAPK has important roles in normal development but is also commonly dysregulated in a variety of human cancers. The biochemistry of this pathway is highly complex, thus hampering drug development efforts and resulting in the inability to develop any drug that directly targets Ras-MAPK to date. 

Immunotherapies that take the brakes off the immune response and direct cytotoxic T lymphocytes (CTLs) to hunt down tumors have revolutionized cancer treatment in the last decade. Stories of patients who are cured by immunotherapy even after exhausting all other treatment options are increasingly common – but unfortunately, only a minority of patients achieve such remarkable benefits. Now, two pressing challenges are to understand why immunotherapy fails in non-responders and to develop new or modified therapies that achieve durable remission for these patients as well.

Cancer cells have a unique ability to rapidly and efficiently remodel their internal composition and metabolic pathways in order to maintain accelerated growth, metastasize and resist anti-cancer therapies. The lysosome, an organelle in the cell that degrades cellular debris, has the ability to control a cancer cell's adaptability. Through processing and recycling different macromolecules, the lysosome serves as an important source of fuel for cancer cell growth and spare parts for remodeling the cell. Dr.

Dr. Maus is engineering the body's own immune T cells to fight deadly brain tumors like glioblastoma. However, in studies of patients with brain tumors, she has found that tumor cells can escape the engineered T cells. She is now redesigning T cells so that they block escape routes used by the tumors. She expects that the engineered cells will be more powerful and may become a new effective treatment for brain tumors.