Welcome to CSTR
A student-led, faculty-supported exploration of the role of physician-scientists in bench to bedside translational medicine. We will examine 5 case studies of translational research using investigators from Penn and industry as preceptors. The course design, which was pilot-tested last year and revised for this year, requires active involvement by all of the students on all of the case studies, working in small teams in which students will rotate as team leader. The course directors and case preceptors have chosen the topics, but the members of each week’s lead team will be responsible for selecting and guiding deliverables. Team roles are described below.
- Skip Brass, MD PhD
- Gregory Podsakoff, MD
- Carsten Skarke, MD
- Ali Naji, MD PhD
- Robert Heuckeroth, MD PhD
Students taking the course
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* Please note the August 23rd start date.
In this chapter we describe three examples of how the interplay between fundamental scientific discoveries and clinical experience has driven the development of innovative treatments in the field of oncology over the past two decades. The first case study concerns the development of the anti-CD20 monoclonal antibody (mAb) rituximab, the first mAb to be approved for therapeutic use and the first single agent to be approved specifically for the treatment of a B cell lymphoma. In recent years, translational research has focused on elucidating the molecular mechanisms underlying rituximab's therapeutic action in order to develop novel agents with enhanced therapeutic profiles. The second case describes how the treatment of a small minority of patients with non-small cell lung cancer expressing chromosomal rearrangements of anaplastic lymphoma kinase was transformed by the clinical development of crizotinib, a small molecule tyrosine kinase inhibitor. However, as with many molecularly targeted treatments, drug resistance to crizotinib usually develops with time, and therefore recent translational research efforts have been directed toward developing agents to overcome resistance mechanisms. Our third case describes how immuno-oncology has evolved as a powerful approach to the treatment of advanced solid tumors. Significant progress in our understanding of the mechanisms underlying tumor-mediated immune resistance has led to the development of antagonist mAbs targeted toward “immune checkpoint” molecules. Several agents, including ipilimumab (anti-CTLA-4) and pembrolizumab (anti-PD-1), have already been approved for the treatment of advanced or unresectable melanoma, where durable, potentially curative responses have been observed in some patients. Translational medicine will undoubtedly play a key role in the future development of rationalized combination strategies in order to improve therapeutic outcomes in a broader range of histologies.
Copyright © 2016 Elsevier Inc. All rights reserved.