Geoffrey Beene Cancer Research Center: 2007 Geoffrey Beene Grant Awards

The following investigators were awarded Geoffrey Beene Cancer Research Center grants in 2007:

Cameron Brennan

Cameron Brennan, MD
Department of Neurosurgery
Project: Applying the Glioblastoma Genome Atlas to Glioma-relevant Signaling

Project Abstract
The genome of glioblastoma, the most common brain tumor in adults, has recently been analyzed in unprecedented detail through the national collaborative project: The Cancer Genome Atlas. Early results point to three distinct subclasses of glioblastoma which differ in gene expression and mutations. We are investigating the activation state of signal transduction pathways among these genomically-defined subclasses of glioma to identify which might be good candidates for therapeutic inhibition.

Renier Brentjens

Renier Brentjens, MD, PhD
Leukemia Service and Hematology Laboratory Service, Department of Medicine
Project: Genetic Modifications to Enhance the In Vivo Survival and Anti-tumor Activity of Gene-Modified CD 19-Targeted T Cells

Project Abstract
T cells are immune cells which may be genetically altered to recognize a patient's own tumor cells. The go of this project is to better design these genetic modifications such that these T cells are more likely to fully eradicate all the tumor cells when injected back into the patients. Data generated from these studies will be used to design better clinical trials for cancer therapy using genetically targeted T cells.

Gabriela Chiosis

Gabriela Chiosis, MA, PhD
Breast Cancer Medicine Service, Department of Medicine
Molecular Pharmacy and Chemistry Program, Sloan Kettering Institute
Project: Chemical/Proteomic Mapping of Cancer-Specific Molecular Therapeutic Targets

Project Abstract
Cancer is complex and no two patients present an identical disease. Because of the diversity of molecular alterations, it is difficult in clinical settings to determine the exact combination of drugs that will result in a best outcome. Our technology offers the promise of identifying, patient-by-patient, the subset of proteins that become aberrant in every cancer cell type/patient tumor tissue. The information gained may be compiled in creating a molecular map of cell- and cancer-specific transformation pathways. This will ultimately allow the physician to design a personalized therapy for patients. Such proteomic map has obvious advantages over the more common genetic signature maps because most anti-cancer agents are small molecules that target proteins not genes, and many small molecules targeting specific molecular alterations are currently in development. Thus, our efforts aim to set the basis for designing combination therapies with better efficacy and less toxicity in the treatment of patients with cancers, and moreover, to define the specific molecular alterations in a particular tumor, facilitating the development of novel molecularly targeted therapies.

Filippo Giancotti

Filippo Giancotti, MD, PhD
Cell Biology Program, Sloan Kettering Institute
Project: A Gain-of-Function Genetic Screen for Human Breast Cancer Metastasis Genes

Project Abstract
We are studying the genetic instructions that induce cancer cells to become metastatic. We have constructed a library of genes from metastatic breast cancer cells, added a molecular tag, and introduced them into non-metastatic cells. The recipient cells have been injected into mice and those that have acquired the ability to metastasize to the lung have been recovered from this organ. Sequencing of the tagged genes has led to the identification of 2 novel genes that play a key role in metastasis. One of the two genes directs cells to make a secreted protein, called Coco, which blocks a signaling receptor, called BMP-receptor. We are isolating new metastasis genes and studying their mechanism of action. We hope that a better understanding of the molecular processes that drive metastasis will lead to the design of drugs that specifically block this process.

Xuejun Jiang

Xuejun Jiang, PhD
Cell Biology Program, Sloan Kettering Institute
Project: PTEN Signaling in Cancer: Novel Regulation and Potential Therapy

Project Abstract
PTEN is a potent tumor suppressor and a master regulator for multiple cell signaling processes. Mounting evidence indicates that PTEN itself is also under precise regulation, and such regulation dictates its signaling and tumor suppressive function. This project aims to understand regulation of PTEN by its ubiquitin ligase NEDD4-1, the potential of NEDD4-1 as a cancer therapeutic target, and potential novel functions of PTEN in other tumor-related signaling events.

Robert J. Klein

Robert J. Klein, PhD
Cancer Biology and Genetics Program, Sloan Kettering Institute
Project: A Genome-wide Association for Pancreatic Susceptibility Loci

Project Abstract
Although it is known that individuals whose relatives have had pancreatic cancer are at greater risk of developing this deadly malignancy, it is not known what particular genes are responsible for this increased susceptibility. Here, we have used individuals from the Memorial Sloan Kettering Familial Pancreatic Cancer Registry to conduct the first stage of a genome-wide association study aimed at identifying common genetic changes responsible for an inherited susceptibility to pancreatic cancer. Our ultimate goal with this research is to identify genes that can be used both to predict who is at risk of developing pancreatic cancer and whose action can be targeted for treatment of this disease.

Mary Ellen Moynahan

Mary Ellen Moynahan, MD
Breast Cancer Medicine Service, Department of Medicine
Project: The Impact of PIK3CA Mutations on the Efficacy of Bevacizumab in Recurrent Hormone-Receptor-Positive Breast Cancer

Project Abstract
In our work funded by the Geoffrey Beene Cancer Research Center, we identified PIK3CA mutations in approximately 1/3rd of invasive breast primary tumors. PIK3CA mutations are associated with favorable clinicopathologic features: lower tumor grade, hormone receptor positive status, HER2 negativity, older age at diagnosis, lower tumor stage, and lymph node negativity. Notably, and in accordance with these favorable pathologic predictors, patients with mutated tumors demonstrate an improvement in overall and breast cancer-specific survival. The protective role imparted by a PIK3CA mutation will significantly affect future clinical trial design for PI3K-targeted therapy.

William Pao, MD, PhD
Project: Characterizing the Cancer Genome in Lung Adenocarcinomas from Patients with Acquired Resistance to EGFR Tyrosine Kinase Inhibitors

Project Abstract
Patients whose lung cancers harbor epidermal growth factor receptor (EGFR) gene mutations have a high likelihood of responding to the tyrosine kinase inhibitors (TKIs), Iressa or Tarceva. However, after about one year, these patients develop progression of disease. In this proposal, we aim to genetically characterize resistant tumors, in order to develop new strategies to treat progressive disease and suppress the development of acquired resistance.

Hans Wendel

Hans Wendel, MD
Cancer Biology and Genetics Program, Sloan Kettering Institute
Project: RNAi Screen to Identify Suppressors and Modifiers of Treatment Response

Project Abstract
Using a process called RNA interference (RNAi) we can selectively inactivate genes in living cells. Moreover, we can use libraries of RNAis to target every gene in the human genome. This technology now allows us to investigate genes whose inactivation contributes to various cancers and may affect therapeutic responses.