Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Enhanced targeted therapy for colorectal cancer

Award Number: R21CA313682
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

Group Awards By:

View Award Description

Enhanced targeted therapy for colorectal cancer - Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. While early-stage diagnosis of this disease offers excellent chances of cure, the disease is often diagnosed after regional or distal spread, with much worse outcomes. The metastatic form of colorectal cancer still lacks satisfactory management options: traditional chemotherapy fails to achieve objective responses in most patients, and immunotherapy is inapplicable in most cases. A large subset of CRC is driven by mutations in BRAF and RAS-family oncogenes, which activate oncogenic MAPK kinase cascade. Targeting the enzymes of this biochemical pathway emerged as a valuable treatment option in other cancers, but is yet to show a comparable benefit in CRC. Prior work of us and others has established an additional pathway that modulates the intensity of the MAPK kinase cascade and may provide resistance to the targeted therapies. The recently uncovered hyper-dependence of that pathway on de novo GTP biosynthesis offers an opportunity to enhance the available targeted therapies by combining them with inhibitors of GTP production. In our preliminary studies, we saw significant synergy in vitro and in vivo between the two classes of drugs against BRAF- and RAS-mutated CRC-derived cell lines. Following on these observations, we will test the ability of ribavirin, a common anti-viral agent and a GTP synthesis inhibitor, to synergize with MAPK kinase cascade inhibitors in suppressing the growth of patient-derived xenografts, which are a more representative model of human disease. Moreover, considering the beneficial and sometimes curative effects of immune therapy in other malignancies, we will elucidate whether the new drug combination could also be effectively combined with inhibitors of immune checkpoints. This will be tested in a model of a metastatic CRC in immunocompetent mice. The treatment-induced changes in the status of various tumorassociated immunocytes will be explored. We will also profile and compare the transcriptional changes occurring in cancerous and normal cells within the tumor microenvironment upon treatment with single drugs or the combination thereof. This will help our understanding of the processes underlying the activity of the new drug combination and would pave the way for further increasing its efficacy and safety. Importantly, the phenomena under our investigation depend on the interaction of tumor cells and the therapeutic compounds with specific microenvironment of the liver, as well as with the immune system. These interactions cannot be accurately modeled in cultured cells, thus necessitating experiments to be performed in animals. Considering that the agents investigated in this study represent drugs already in human use for other indications, the success of this project will create an opportunity to expediently translate the findings into clinics, finally providing effective and generally applicable treatment options for this deadly disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $446,112 )
2026	2026	HEALTH RESEARCH, INC.	665 ELM ST	BUFFALO	NY	14203	ERIE	USA	Cancer Treatment Research	000	1	7/3/2026	NEW	$446,112
														Subtotal = $446,112

Grand Total All Awards = $446,112

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Enhanced targeted therapy for colorectal cancer

Award Number: R21CA313682

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer