Program Leader: Vern Schramm
Co-Program Leader: Roman Perez-Soler
Experimental
Therapeutics at the Albert Einstein Center for Cancer Research (AECC) is the
programmatic home for basic and clinical investigations encompassing a broad
spectrum of antineoplastic modalities. Two major areas of research in the drug-development
arena are: (1) drug design: the
development of novel agents for the treatment of cancer based upon
transition-state principles, chemical library screening, rationale agent
design, and novel proteins. (2) immunotherapeutics: focused on understanding
the mechanisms by which tumors escape immune detection and elimination and the
development of agents that reactivate the immune system. Therapeutics
developments are directed to novel targets identified in this and other AECC programs.
Research in Experimental Therapeutics during the last six years has resulted in
a spectrum 181 cancer-related patent filings, 21 license agreements with
pharma, the formation of 13 start-up companies and the recent approval of a
drug for the treatment of T-cell leukemia/lymphomas in Japan. Transition-state
analogue inhibitors focused on novel targets are in the pipeline, including
several that impact epigenetic processes.
Based upon an understanding of the structure and function of BAX, small
molecule activators of BAX, developed at AECC, induce cancer cell apoptosis and
are activity in vitro and mouse
xenografts while BAX inhibitors prevent the cardiotoxicity of cytotoxic and
targeted anticancer agents. A novel family of immune checkpoint co-inhibitory
molecules has been identified, their expression in human cancers documented,
and robust development of inhibitory antibodies is underway at AECC and in
collaboration with pharma. A new technology is in development consisting of a specific
antigenic recognition peptide together with stimulatory T-cell signals that expand or differentiate clinically-relevant T-cell clones with
minimal impact on the general T-cell repertoire. This novel approach minimizes
off-target side effects associated with current clinical immunotherapies. There
are robust capabilities in protein production, small molecule and fragment
screening, x-ray crystallography, NMR, and mass spectroscopy with
bioinformatics and systems and computational biology support based in this
program. Members in this program take the lead in AECC shared resources. Drug
development efforts are supported by a developing Chemical Synthesis Shared
Resource. Disease-focused working groups continue to interact with laboratory
scientists to foster translational studies. Members of this program conduct all
clinical therapeutic trials at AECC. There is an active Phase I/II effort, in
part related to the translation of leads in this and other programs into
investigator-initiated studies by this program.
AECC members play important roles in ECOG-ACRIN, NRG, GOG, COG, and the
AMC. There are currently 52 members from 21 departments.
Selected Achievements of the Experimental Therapeutics program
Members
Member Joseph Sparano in the news:
Joseph A. Sparano, MD, on Early-Stage Breast Cancer: Findings on the Tumor Microenvironment from Harborside Press on Vimeo.