DCTD’s Cancer Therapy Evaluation Program Convenes 2018 Symposium on Mechanisms of Cancer Drug Resistance and Sensitivity

On October 4-5, 2018, the Cancer Therapy Evaluation Program (CTEP) held its second Symposium on Mechanisms of Cancer Drug Resistance and Sensitivity (agenda). The symposium brought together research scientists, cancer clinicians, pharmaceutical companies, NIH grant recipients, and NCI staff to highlight and discuss research on:

• Sensitivity to specific types of therapy
• Circumventing the development of cancer resistance to drugs
• Effectively treating cancers that have become refractory to treatment

Overall Goal

Feature preclinical research focused on innovative strategies to understand and combat mechanisms of tumor resistance and to exploit tumor sensitivity to anti-cancer therapies.

Keynote Speakers

• Carlos Arteaga, MD, UT Southwestern — Discovery of targetable mechanisms of endocrine resistance in estrogen receptor positive, HER2-negative breast cancer
• Charles Sawyers, MD, Memorial Sloan Kettering — Lineage plasticity in cancer

Meeting Session Highlights

• Insights into Immunomodulatory Drug Resistance
  • How cancer cells become resistant to the new immune checkpoint inhibitors that are becoming standard therapy for many cancers
  • Advances in modeling of the tumor immune microenvironment and defining T cell states associated with response to checkpoint immunotherapy
  • Genetic mechanisms of intrinsic and extrinsic resistance to checkpoint blockade
• The Tumor Microenvironment in Drug Resistance and Sensitivity
  • Effect of microenvironmental changes (damage responses in the inflamed tumor microenvironment that can augment cancer resistance to therapy) with tyrosine kinase inhibitors
  • Combination therapy to possibly overcome intrinsic tumor resistance and the resistance mediated by the tumor microenvironment
• Emerging Pre-Clinical Models to Study Drug Resistance and Sensitivity
  • Use of sophisticated organoid and patient-derived xenograft tumor models in preclinical studies of cancer sensitivity and resistance
  • Large-scale screening of novel agents with new models for discovery in anticancer therapy
• Resistance Biomarkers and Pathways
  • Discoveries in genetic and epigenetic pathways have broadened understanding of how cancer cells adapt to cancer therapeutics
  • Stem cell pathways driving cancer survival
  • Biomarkers of resistance observed in clinical biopsies of patients undergoing therapy on clinical trials
• Large Dataset Analysis in Drug Resistance Research
  • Discovery of new mechanisms of cancer resistance to therapy by unbiased large-scale genomic analysis of cancers in patients with new targeted agents
  • Techniques to analyze and integrate data from large data sets and functional assays to corroborate the importance of the discovered pathways
• Poster Session
  • NCI and non-NCI presenters summarized their discoveries in cancer drug resistance
  • Networking and discussion between young investigators and established researchers