The Rubenstein Center brings together a multidisciplinary team of basic, translational, and clinical scientists to pursue groundbreaking research focusing on a broad range of questions relevant to our understanding of pancreatic cancer as well as to our ability to control the disease. For example, our scientists conduct studies focused on the epidemiology, early detection, chemoprevention, and therapeutics of pancreatic cancer as well as the identification of new imaging techniques and circulating biomarkers. In addition, the Rubenstein Center is pioneering advanced genomics techniques to yield new insights about the clonal heterogeneity of pancreatic tumors and find new ways to overcome mechanisms of drug resistance.
Rubenstein Center experts provide collaborative consultation and assist the Memorial Sloan Kettering research community in acquiring and analyzing pancreatic cancer biospecimens, including fresh frozen and paraffin-embedded tumor tissue; customized tissue microarrays; tumor DNA, RNA, and protein; ctDNA and circulating tumor cells; and genetically engineered mouse models.
Project Title: Investigation of BRCAness Phenotype in Pancreatic Cancer
Investigators: Nicolas Lecomte
Collaborators: Steven Leach & Nadeem Riaz
Project Description: Our project seeks to identify new molecular determinants of BRCAness in Pancreatic cancer. Given the heterogeneous and unclear mechanisms that can drive BRCAness, we ambition do perform a comprehensive analysis of ex-vivo models of pancreatic cancer. Enabled by the derivation of a large repository of patient-derived organoids, our broad-based approach aims to identify patients with BRCAness phenotype, as revealed by exquisite sensitivity to platinum-based agents or PARPi and defects in homologous recombination (HR) and concomitantly to perform a multidimensional characterization including whole-exome (WES) and transcriptome sequencing (RNAseq) and drug sensitivity profiling. Ultimately we envision that the identification of critical determinants of BRCAness in pancreatic cancer will broaden the scope of patients that most likely may benefit from such targeted therapy. Additionally, comprehensive characterization of tumors in which HR defect exists without response to platinum or PARPi might lead to define critical predictive markers of such therapy efficacy.
Project Title: A Randomized Phase II Study of Gemcitabine, Cisplatin +/- Veliparib in Patients with Pancreas Adenocarcinoma and a Known BRCA/ PALB2 Mutation (Part I) and a Phase II Single Arm Study of Single-Agent Veliparib in Previously Treated Pancreas Adenocarcinoma (Part II)(NCI #8993)
Investigators: Eileen O’Reilly
Co-PI: David Kelsen, Maeve Lowery
Project Description: The purpose of the study is to evaluate a combination of gemcitabine and cisplatin with or without veliparb (ABT-888) in patients with advanced pancreas cancer. Gemcitabine and cisplatin are standard drugs used to treat pancreas cancer and are both FDA-approved. Veliparib is a new medication belonging to a class of drugs called PARP inhibitors. Veliparib is an experimental drug. Veliparb is not FDA-approved and is in clinical trial testing for patients with various cancers. In this trial we are comparing standard therapy to standard therapy plus veliparb. We want to find out what effects, good and/or bad the combination has in patients with pancreas cancer with a BRCA or PALB2mutation.
Project Title: Circulating Tumor Cell and Tumor Tissue Models for Predicting Effective Pancreatic Cancer Treatment
Investigators: PI: Kenneth Yu
Co-PI: Eileen O’Reilly
Collaborators: CSHL (Tuveson), Adera Labs, LLC.
Project Description: This study involves prospective CTC and patient derived organoid drug testing in advanced PDAC patients receiving FOLFIRINOX or gem/nab-P chemotherapy. The purpose of the study is to develop a test to predict response of cancer to different chemotherapy regimens using tumor cells from biopsied blood. We will collect blood samples and biopsies from patient’s cancer. Prior research has found that tumor cells can be collected from the blood of patients with pancreatic cancer. We have found ways to isolate and study cancer cells using blood test. Prior research has also found that tumor cells from patient tumors can be grown in the laboratory. In collaboration with Cold Spring Harbor Laboratory (CSHL), we will test a number of drugs against the cells and see how they respond. We will also see how patient respond to their chemotherapy to see if our prediction matches.