Therapeutics Discovery

Despite major recent advances in oncology drug discovery, including the development of innovative targeted, immune and cell-based therapies, there remain many opportunities to improve outcomes for patients with cancer. Some may not benefit from available treatments, and others may have highly aggressive or drug-resistant cancers that require new options.

As part of MD Anderson’s commitment to bring our patients the most effective, safest treatments possible, MD Anderson established the TRACTION platform - a state-of-the-art translational biology engine to address the challenges of drug discovery by enabling highly innovative, collaborative oncology research.

TRACTION - Translational Research to AdvanCe Therapeutics and Innovation in Oncology - is a core component of MD Anderson’s Therapeutics Discovery Division, a unique group of clinicians, researchers and drug discovery scientists working to develop innovative cancer treatment options, inspired by the needs of patients and guided by the expertise of MD Anderson physicians.  

TRACTION is one of the research platforms launched by MD Anderson’s Moon Shots Program® to provide unique expertise, technical support and novel infrastructure to enable impactful research projects. The Moon Shots Program is a collaborative effort to rapidly develop scientific discoveries into meaningful clinical advances that save patients’ lives.

Tim Heffernan, Ph.D., executive director of TRACTION, spoke with Cancer Frontline about the platform and how it is contributing to MD Anderson’s goal of Making Cancer History.

Q: Can you briefly describe the work of the TRACTION platform?

A:  TRACTION functions as an industrialized translational research platform with the overarching goal of accelerating the translation of new knowledge into clinical impact.

Our work covers a few major themes that aim to address several challenges we face in oncology drug discovery and development - namely new targets, new mechanisms, new drugs and better predictive platforms.  We take a comprehensive approach that includes:

·         Deploying disruptive technologies to identify and evaluate novel tumor dependencies

·         Performing fundamental mechanistic biology to explore new therapeutic or target hypotheses

·         Leveraging patient-centric translational platforms to identify which patients will most likely benefit from a given therapy. 

Through our investment in patient-centric research, we have developed the infrastructure, platforms and capabilities to enable collaborative translational research. By partnering with the drug discovery engines within Therapeutics Discovery, we aim to advance a portfolio of new medicines for our patients.

Q: How is the TRACTION platform organized to carry out this work?

We’re organized into cross-functional units that guide our research and development.  Our “Discovery and Innovation” group employs technology platforms and advanced data analytics to evaluate new therapeutic concepts that fuel our early stage drug discovery pipeline. This group evaluates trends emerging from clinical data and seeks to understand the fundamental biological mechanisms of drug response, tumor heterogeneity and tumor evolution to uncover novel therapeutic concepts.

Our “Target Biology” group executes mechanistic studies on specific targets to advance our internal drug discovery and development portfolio from concept to IND filing. These studies inform on target biology, adaptive responses and mechanistic co-extinction, ultimately allowing us to formulate definitive hypotheses to guide clinical development.

Lastly, our “Translational Biology” team supports drug development by providing industry-scale disease modeling, translational biology, in vivo pharmacology and biomarker development capabilities. Through integration with disease site experts, this team curates a comprehensive, patient-centric toolbox of preclinical models for studies that guide clinical development and identify appropriate biomarkers of response.

Q: TRACTION is a new name for the platform. How does this name better reflect your goals and scope of work?

A: Our rebranding from the Center for Co-Clinical Trials to TRACTION more accurately reflects our comprehensive approach to support research-driven patient care. Early on, we had established a number of translational partnerships with Moon Shots disease sites, and we soon realized the opportunity to expand our efforts into early discovery by leveraging our unique access to clinical and research data.

Thus, we expanded our group, enhanced our capabilities and fostered partnerships with other enabling platforms, such as APOLLO and TRA. Through these partnerships, we can better deploy our resources and capabilities to uncover novel concepts that could eventually uncover new clinical hypotheses and/or feed our Therapeutics Discovery pipeline. Our expansion has fostered collaborations across the institution to explore novel concepts in rare cancers, early disease, drug resistance, tumor evolution and immuno-oncology.

Q: How is your patient-driven translational approach unique from other companies or groups working in this area?

A: The fundamental differences are access, integration and scientific engagement. There are many organizations performing translational research, but at MD Anderson, we benefit from the fact that research begins and ends with the patient.

Within TRACTION, we implement reverse translation through unique and unprecedented access to clinical samples, profiling data and treatment outcomes to prioritize our next experimental question.  Integration across MDA is essential as our programs are enabled through symbiotic relationships that we have developed across basic-, clinical- and applied-research disciplines, where we benefit from the expertise across MD Anderson to drive innovation around programs with the greatest probability of catalyzing transformative advances.

A third level of differentiation is scientific engagement. We are not a core facility nor a fee-for-service organization. Rather, the collaborations that we establish are true partnerships where we ensure that all parties involved are committed to maximize the clinical impact of new therapeutics.

Q: You recently announced a strategic partnership with Boehringer Ingelheim.  Can you discuss how corporate partnerships contribute to your mission?

A:  Corporate partnerships are essential to our mission.  We work closely with our colleagues within Strategic Industry Ventures to identify potential partners and facilitate a discussion focused on a clinically translatable research plan.

Our decision to partner is based on several factors. Most importantly, we look for alignment with an area of strength within TRACTION and MD Anderson. We’re most interested in partnerships that could complement our internal portfolio within Therapeutics Discovery, and most importantly, have the potential to provide MD Anderson patients with new therapeutic options. 

In addition to our patient-centric translational platforms, our ability to engage research and clinical faculty throughout the lifespan of a project are key factors that differentiate us from other translational organizations. Our partners value that, through integration, we bridge the gap between preclinical discovery and clinical development by providing a direct line of sight to the clinic.

Q: How has your team collaborated across the institution to achieve significant patient impact?

A: TRACTION supports the mission of MD Anderson by providing infrastructure, capabilities, and resources to evaluate translational hypotheses generated by investigators across the institution.  Over the last six years, we have collaborated with multiple Moon Shots to generate preclinical data that have informed the design of several clinical trials, including novel and repurposed drugs as single-agent and combination therapies.

We have built on these collaborations to establish a number of exciting efforts ongoing with various Moon Shots teams. These programs span the drug discovery and development continuum, from target discovery through preclinical evaluation of new therapeutics. Indeed, Moon Shots collaborations have been critical in our success to advance therapeutic concepts within our own Therapeutics Discovery Division, most notably, IACS-10759 and IPN-60090, two clinical programs advanced in partnership with the Institute for Applied Cancer Science.

I would emphasize that our collaborative efforts are not limited to Moon Shots programs.  We have established relationships across the institution in support of highly innovative science aimed at addressing unmet clinical needs.  In line with our expanded scope and reach, TRACTION has recently deployed resources to support two important MD Anderson initiatives.

In partnership with Andy Futreal, Ph.D., and Ignacio Wistuba, M.D., co-leaders of the APOLLO platform, we are providing support to discover and develop new therapeutic concepts emerging from the Rare Tumor Initiative.  A second area of interest, in collaboration with Hussein Tawbi, M.D., Jing Li, M.D., Ganesh Rao, M.D., and Michael Davies, M.D., Ph.D., focuses on enhancing our understanding of the biology of brain metastases to identify novel strategies that could be advanced in the new MD Anderson Brain Metastasis Clinic.  Both of these initiatives rely on multidisciplinary teams that represent unique areas of strength at MD Anderson.

With the support of the Moon Shots Program and its investment in team science, together with the tremendous collaboration we see across MD Anderson, we aim to accelerate the pace of discovery. We already have helped advance several therapies into clinical trials, and we will continue to execute a multidisciplinary approach to overcome the traditional challenges in cancer drug discovery – all to bring new therapies to our patients that need them most.