# Targeting casein kinase 1-alpha for cancer therapy

> **NIH NIH K08** · STANFORD UNIVERSITY · 2022 · $206,539

## Abstract

Project Summary
Colorectal cancer is the second leading cause of cancer-related death in the United States annually. Despite
recent advances in our understanding of the molecular underpinnings of advanced colorectal cancer,
chemotherapy remains the mainstay of treatment, with limited efficacy. Mutations activating the WNT-signaling
pathway are known to drive the majority of colorectal tumors, but no effective therapeutic strategies targeting
this pathway have been developed to date. Analysis of genome-wide genetic loss of function screens in cancer
cell lines has revealed that colorectal cancers that depend on beta catenin for survival are also vulnerable to
loss of casein kinase 1-alpha (CK1A). Direct therapeutic targeting of CK1A is unproven, however, and it is
unknown whether there is a direct functional link to beta catenin signaling in colorectal cancer. This proposal
builds on preliminary findings to dissect the mechanism of CK1A dependence in colorectal cancer. We will use
complementary genetic and pharmacologic approaches to 1) determine the relationship between loss of casein
kinase and beta catenin activity, 2) establish the therapeutic efficacy of targeting CK1A in preclinical models,
and 3) elucidate downstream phosphorylation targets of CK1A. Results of these investigations have the
potential to establish a new treatment approach for colorectal cancer. Dr. Steven Corsello’s long-term goal is to
apply insights from systematic cancer vulnerability screens to advance cancer drug discovery for the treatment
of gastrointestinal cancers. Dr. Corsello, based at the Dana-Farber Cancer Institute and the Broad Institute, is
mentored by Dr. Todd Golub, a pioneer in cancer genomics, and Dr. William Hahn, a leader in cancer biology
and functional genetic screening. An expert career advisory committee consisting of Dr. Nathanael Gray, Dr.
Adam Bass, and Dr. Brian Wolpin will provide additional mentorship in drug discovery, disease models, and
clinical translation. With input from his mentors, Dr. Corsello has developed a comprehensive five-year training
plan incorporating laboratory training, didactic studies, and scientific community engagement.

## Key facts

- **NIH application ID:** 10445233
- **Project number:** 5K08CA230220-06
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Steven Muntean Corsello
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $206,539
- **Award type:** 5
- **Project period:** 2018-07-06 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445233

## Citation

> US National Institutes of Health, RePORTER application 10445233, Targeting casein kinase 1-alpha for cancer therapy (5K08CA230220-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10445233. Licensed CC0.

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