Federal Grant Award Summary

The National Cancer Institute (NCI) awarded a $730,398 Project Grant to Sloan-Kettering Institute for Cancer Research under the Cancer Treatment Research program (CFDA 93.395) effective April 1, 2026, through March 31, 2031. This research initiative focuses on understanding and overcoming treatment resistance in locally advanced rectal cancer (LARC) patients undergoing total neoadjuvant therapy (TNT)—a combined treatment regimen consisting of radiation therapy, chemotherapy, and surgical intervention or organ-preservation strategies. The primary deliverable is the identification and development of therapeutic interventions targeting tumor regenerative cells (TRCs), specifically those expressing the L1CAM (neural cell adhesion molecule) marker, which are implicated in both local tumor regrowth and distant metastatic recurrence following TNT.

The funded research will employ integrated genomic and transcriptomic analysis of pre-treatment rectal tumors, mechanistic studies utilizing patient-derived organoid models and novel mouse models of LARC, and single-cell transcriptomic analysis of metastatic colorectal cancer specimens. The project will culminate in the development and preclinical testing of novel L1CAM-targeting antibody-drug conjugates (ADCs) in highly clinically relevant patient-derived organoid and orthotopic xenograft mouse models. These scientific products are designed to address the critical clinical need for improved local and distant disease control, where approximately 20% of patients with clinical complete response experience local regrowth and 15% develop fatal distant metastatic recurrence, with only 50% achieving successful organ preservation.