NCI Webinar Series: Novel Chemical Approaches for Targeting Fusion Oncoproteins

The recordings of the individual webinars are posted below.

Read the workshop proceedings (Verma, 2024).

Overview

A joint effort between DCTD's Developmental Therapeutics Program and NCI's Division of Cancer Biology, this webinar series enhanced understanding within the NCI and the research community of opportunities for targeting fusion oncoproteins through emerging chemoproteomic methods.

Background and Research Challenge

Research has advanced our understanding of the biology underpinning pediatric fusion oncoproteins. For example, menin inhibitors for KMT2A-rearranged leukemias achieved proof-of-concept for the blockade of transcription factor fusion oncoprotein action, and agents targeting the menin-MLL protein-protein interaction are in clinical testing. However, current progress towards targeting additional transcriptional factor fusion oncoproteins has been limited. Consequently, the absence of small molecule therapeutics targeting fusion oncoproteins limits improvement in outcomes for pediatric patients with cancer.

Opportunities

Expanding chemoproteomic tools and capabilities creates opportunities for progress in directly targeting fusion oncoproteins and/or their critical dependencies. The External Scientific Advisory Committee for the Cancer Moonshot-funded Fusion Oncoproteins in Childhood Cancers (FusOnC2) Consortium highlighted this point in its recommendations to the NCI.

Webinar Series Highlights

This webinar series addressed the challenges and opportunities in the field by highlighting:

• Innovative screening platforms to identify new targets and novel chemical matter
• Emerging strategies for developing chemical degraders and irreversible inhibitors, including use of computational based and AI tools to facilitate their molecular design
• Successes in translating candidates identified from target-based and phenotypic approaches

Webinar Recordings

Session Information	Link to Recording
Session I - August 19 Brandon Turunen, PhD, GSK Chemical Biology Platforms to Drug the Undruggable NCI Moderator - Sharad Verma, PhD	Recording
Session II - August 26 Angela Koehler, PhD, Massachusetts Institute of Technology Attenuating Oncogenic Transcription NCI Moderator - Malcolm Smith, MD, PhD	Recording
Session III - September 9 John "Jay" Schneekloth Jr, PhD, NCI Tools and Tactics for Targeting RNA with Small Molecules NCI Moderator - Joel Morris, PhD	Recording
Session IV - September 16 Fleur Ferguson, PhD, University of California, San Diego Application of Targeted Protein Degradation to Fusion Oncoproteins NCI Moderator - Sharad Verma, PhD	Recording
Session V - September 23 Zoran Rankovic, PhD, St. Jude Children's Research Hospital Targeted Oncoprotein Degradation for the Treatment of Pediatric Cancers NCATS Moderator - Craig Thomas, PhD	Recording
Session VI - September 30 Huan Rui, PhD, Amgen Computational Tools and Strategies for Rational Degrader Design NCATS Moderator - Min Shen, PhD	Recording
Session VII - October 7 Tomek Cierpicki, PhD, University of Michigan Development of NSD1 Inhibitors Targeting NUp98-NSD1 Fusion Leukemia NCI Moderator - Morgan O'Hayre, PhD	Recording
Session VIII - October 14 Matthew Disney, PhD, UF Scripps Biomedical Research Ribonuclease Targeting Chimeras for the Selective Targeting of Oncogenic RNAs NCI Moderator - Sundar Venkatachalam, PhD	Recording
Session IX - October 21 Paul Workman, PhD, FRS, FMedSci, Institute of Cancer Research, UK Discovery of Clinical Cancer Drug Candidates by the Target-Based Approach and Phenotypic Screening NCI Moderator - Beverly Teicher, PhD	Recording

Contact: Sharad Verma sharad.verma@nih.gov, or Keren Witkin keren.witkin@nih.gov