The Belfer Center's Drug Discovery platform focuses on the steps leading up to first-in-human trials, from target discovery to IND submission.
Belfer investigators complement our industry partners' clinical development expertise by bringing to the table leading-edge basic discoveries, clinical expertise and knowledge, and advanced biological models—including clinical samples and unique disease models—geared toward basic and preclinical drug development. As a result, we address a variety of critical drug-discovery needs:
- Generation and validation of hypotheses regarding responder populations
- Identification and validation of predictive, response, and pharmacodynamic biomarkers
- Identification of novel targets by leading-edge approaches
- Target validation using unique models and technology
Therapeutic agents that harness the immune system have shown remarkable efficacy and durability in populations with few treatment options. However, we have limited understanding of how these drugs work and why they work only in some patients and not others.
Using novel insights from both preclinical models and patient samples, and leveraging the Belfer Center's distinctive capabilities (see below), the Immuno-Oncology Platform's scientists collaboratively seek new drugs and new drug combinations, as well as translational biomarkers that correlate with response and resistance.
- Tumor immune infiltrate profiling in patient and mouse model tumors
- Development and utilization of proprietary in vivo models for immunomodulatory drug assessments
- In vivo and in vitro target identification
Translational medicine—collaborative preclinical research that matches the right patients to the right drugs in the right biological and genomic context—is an overarching theme at the Belfer Center. Belfer Center researchers leverage 40 years of cumulative pharmaceutical drug discovery and disease-area expertise to create a path for rapid, efficient clinical development of cancer therapeutics.
Working in close collaboration with DFCI investigators who are world-renowned disease area experts, we delineate clinical development strategies for novel oncology therapeutics by:
- Understanding key molecular drivers of cancer subtypes and the genetic factors of drug response to inform potential clinical indications for drug development
- Understanding the tumor immune microenvironment
- Exploring patient identification strategies in potential indications to delineate and test a responder ID hypothesis
- Optimizing dose, schedule, biomarker determinations, and combinations in clinically relevant model systems through in vivo pharmacology
Our translational science guides the selection of agents, clinical indications, patient-responder identification, biomarkers, and therapeutic strategies in focused clinical indications.
Experimental Therapeutics Core
The Experimental Therapeutics (ETx) Core is a preclinical resource for Dana-Farber Cancer Institute researchers and their collaborators. The core provides comprehensive high-quality in vivo pharmacology expertise and capabilities that support translational drug discovery and drug development research, including preclinical studies of:
- Efficacy and tolerability of therapeutic agents alone or in combinations
- Tumor model development
- Mechanism of action
- Target identification and validation
Translational Research Laboratory
Translational Research Laboratory (TRL) investigators focus on the discovery and validation of blood-based biomarkers through a unique platform, the "liquid biopsy." These non-invasive tests leverage advanced genomic techniques to study cell-free tumor DNA harvested from blood to improve our understanding and ability to treat many cancer subtypes (e.g., lung, skin, colorectal, and prostate cancers). For instance, liquid biopsies may help:
- Noninvasively identify patients who would benefit from genotype-directed therapies (e.g., EGFR-mutant lung cancer patients)
- Assess response in patients treated with emerging immunotherapies (e.g., anti-CTLA-4, anti-PD-1)
- Evaluate drug responses in real-time and non-invasively
- Real-time and noninvasive identification of emerging resistance
Using this technology, the TRL can help accelerate cancer drug development by integrating industry-grade research assays and biomarkers in active clinical trials, including those being conducted at Dana-Farber Cancer Institute.