Damon Runyon News

Hematopoietic stem cell transplantation (HCT) is a potentially curative procedure for patients with hematologic malignancies who are otherwise incurable with conventional therapies. Despite advances in post-transplant care, the morbidity and mortality of complications such as graft versus host disease (GVHD) and infections remain significant limitations, and hinder the application of this life-saving procedure. Infection and GVHD are influenced by the immune system, which in turn is regulated by the bacterial contents of the human gastrointestinal tract.

Myeloproliferative neoplasms (MPN) are a type of blood cancer sometimes considered to be "pre-leukemias" which can progress to leukemia and are also lethal cancers in their own right. A population of rare hematopoietic stem cells (HSC), called MPN disease-propagating cells, typically harbor mutations that cause the cells to overproliferate. These mutated HSC produce abnormal cancerous blood cells that over time can eliminate the normal blood cells in the bone marrow.

Lung cancer is responsible for more cancer-related deaths in the U.S. and worldwide each year than any other cancer. Historically, patients with advanced metastatic disease have been treated with conventional chemotherapy. Recently, however, subsets of lung cancer patients have been identified with specific molecular alterations that allow for treatment with rationally chosen targeted therapies. One molecular subset of lung cancer is characterized by the presence of alterations in a protein called ALK tyrosine kinase.

Approximately 10-15% of pediatric and adult patients with B-cell acute lymphoblastic leukemia (B-ALL) have a high-risk form of the disease characterized by rearrangements of a gene called CRLF2. Alterations of this gene result in increased expression of the CRLF2 protein and promote leukemia development. When treated with conventional chemotherapy, patients with CRLF2 gene alterations do poorly. Their leukemias are dependent on an enzyme called JAK2 for survival, yet no targeted therapies with proven efficacy are currently available. Dr.

Kaposi sarcoma (KS), a potentially fatal cancer especially in immunodeficient individuals, is caused by human herpes virus-8 (HHV-8), a carcinogenic agent declared by the World Health Organization. Human genetic variability may account for the variability in the clinical outcome of HHV-8 infection. Dr. Jackson aims to discover novel genetic alterations underlying childhood KS and to understand how specific gene defects drive KS in conjunction with HHV-8.

Patients with relapsed blood cancers after allogeneic stem cell transplant are often treated with donor lymphocyte infusion (DLI), a type of immunotherapy that boosts the anti-tumor response and aims to induce cancer remission. The success of DLI varies from patient to patient. Dr. Bachireddy aims to investigate the determinants of DLI success and failure by studying the leukemic and immune cells during response to immunotherapy.

Despite recent advances, lung cancer remains the leading cause of cancer related death in the United States, and there is an urgent need for new therapies. The most successful treatments for lung cancer to date are the targeted drugs erlotinib and crizotinib. These drugs block tumor growth in cancers that respectively harbor either mutations in EGFR or translocations in the ALK gene. Unfortunately, only a minor fraction of patients’ tumors have EGFR mutations or ALK translocations; therefore, the vast majority of patients lack an effective targeted therapy.

Dr. Adamson [HHMI Fellow] is using large-scale genetic approaches to map the regulatory networks responsible for maintaining molecular equilibria inside human cells. An important question in cancer research is how cancer cells adapt to abnormal growth environments and proliferate under stress. Systematic characterization of the processes that maintain these equilibria will be critical for better understanding cancer formation and growth.

Many prostate cancers initially respond to treatments that block the hormone testosterone, thus halting tumor growth. These treatments block testosterone by targeting a molecule called the androgen receptor (AR). However, patients often develop resistance to these drugs, giving rise to an aggressive AR-independent form of prostate cancer. Often under-recognized, AR-negative neuroendocrine prostate cancer (NEPC) currently represents approximately 25% of advanced prostate cancers.