Damon Runyon News

Brain metastases are the most common tumor in the brain, most frequently originating from melanoma and carcinomas of the lung and breast. Of patients who develop brain metastases, approximately half succumb to the cancer in their brain. Unfortunately, treatment options are limited, and most current clinical trials in the US exclude patients with brain metastases. Dr. Brastianos recently completed a large study to understand the genetic changes that occur in brain metastases. She identified genetic alterations in brain metastases that predict sensitivity to targeted therapies.

Non-small cell lung cancer (NSCLC) is a particularly aggressive type of lung cancer, and mesothelioma is an equally aggressive cancer of the lining of the lung. Despite recent therapeutic advances, approximately 190,000 and 3,000 Americans respectively succumb to these cancers each year, emphasizing the urgent need for more effective treatments. Therapies that use cancer-recognizing immune T cells are especially promising. T cells specifically bind particular tumor-associated molecules (antigens) and kill bound cancer cells through proteins called "T cell receptors" (TCRs).

Many cancers are treated with chemotherapies that affect DNA repair, such as platinum chemotherapy, and some patients derive significant benefit from these agents. However, the underlying genomic features that drive selective response to these treatments is incompletely characterized. Dr. Van Allen aims to blend precision cancer medicine principles with DNA repair treatments and enhance cancer care. He will do so by studying the genomics of response to existing and emerging DNA repair therapies in preclinical models as well as patients across different tumor types.

It remains unclear why some patients' tumors can be cured with chemotherapy, whereas other tumors that appear to be nearly identical are completely chemoresistant. Dr. Gutierrez focuses on this issue in a particularly high-risk subset of T-cell acute lymphoblastic leukemia, a disease that most commonly affects older children and young adults. His goals are to define the molecular basis of resistance to conventional chemotherapy in patients with this disease, and to leverage this knowledge to develop a therapeutic strategy to restore chemosensitivity.

Dr. Brody aims to develop a novel treatment approach for patients with advanced-stage lymphoma, by which the patient's immune system is trained to recognize and eliminate his/her own cancer. This approach, an "in situ vaccine," recruits and activates specific immune cells, dendritic cells (DC), at the location of the treated tumor - where they can then educate the rest of the immune system to recognize and eliminate tumors throughout the body.

Head and neck cancer is a lethal malignancy that can arise in the mouth, throat, voice box, and related areas. These tumors are squamous cell cancers that are, in many cases, caused by tobacco use or human papillomavirus (HPV) infection. Head and neck cancers have many molecular similarities with squamous cell cancers of the lung and esophagus. Dr. Morris is studying a poorly understood gene called FAT1, which is frequently altered in head and neck cancer (as well as lung and esophageal cancer). He has found that this gene, in its normal state, prevents tumor development.

Hematopoietic stem cell transplant is the preferred and only curative treatment for most patients with acute myeloid leukemia (AML); however, a significant percentage of patients will eventually relapse. A novel effective therapy option is therefore urgently needed. Dr. Budde [The Jake Wetchler Foundation for Innovative Pediatric Cancer Research Clinical Investigator] is testing a new strategy that uses patients' own immune T cells, which have been modified to specifically target and kill leukemia cells.

Myeloproliferative neoplasms (MPNs) are a group of blood cancers in which a malignant cell population proliferates out of control. Myelofibrosis (MF) is one type of MPN in which the bone marrow becomes replaced by scar tissue, leading to progressive failure of normal blood cell functions and ultimately death, on average five years after initial diagnosis. MPNs, including MF, can evolve to secondary acute myeloid leukemia (sAML), which is almost invariably fatal. There is no reliable curative treatment currently available for MPNs or MF.

Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive lymphoma in adults.  Unfortunately, current therapies typically fail in nearly half of these patients. Dr. Alizadeh proposes a novel treatment strategy for this disease: to characterize and isolate premalignant stem cells before they transform into cancer cells. He has found that expression of a single oncogene called BCL6 is capable of reprogramming these cells from normal cells to aggressive malignant cells. He aims to define the specific genetic alterations that can give rise to this cell reprogramming.

Dr. Abdel-Wahab [Edward P. Evans Foundation Clinical Investigator] specializes in specific blood cancers called myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). He recently identified mutations in the gene ASXL1 in patients with MDS and AML. ASXL1 is one of the most commonly mutated genes in MDS patients, and these mutations occur in up to 20% of AML patients. ASXL1 mutations result in a worsened overall survival in MDS and AML patients and contribute to chemotherapy resistance in AML.