Current therapies for colon cancer rely primarily on drug combinations of cytotoxic chemotherapy and are often unable to prevent tumor resistance and recurrence. While several biologic agents targeting growth factors have been approved in combination with chemotherapy, there is still a great number of patients that typically do not respond to these standard-of-care treatments.
This proposal will pursue the development of a novel class of non-cytotoxic small molecules for the treatment of colon cancer. These new agents have been designed to mimic the actions of endogenous anti-inflammatory molecules that can suppress the chronic inflammatory microenvironment found in the tumor milieu. Chronic inflammation is required for maintaining tumor growth, angiogenesis, and metastasis. The suppression of inflammation ultimately deprives the tumor of essential growth elements, resulting in cellular apoptosis and tumor death. Preliminary studies on this innovative concept show great translational potential for the treatment of colon cancer.
This proposal seeks to pursue the preclinical development of this type of biomimetic small molecule involving the use of a novel nano-encapsulation method for oral and parenteral formulation. The main objective is to validate a proof of concept for the use of these agents as potential therapeutics for colon cancer. The proposal has two specific aims: (a) Scale-up the lead molecule that has been identified, and determine the in vivo optimal dosage that leads to maximum antitumor efficacy in an immunotherapy-responsive mouse model. (b) Investigate the mechanism(s) responsible for the cancer immunotherapeutic effects of the lead molecule.
Overall, based on the recognition that persistent inflammation is a key hallmark of cancer, the development of the proposed nano-encapsulated small molecule immunotherapeutic shows great promise in colon cancer and other inflammation-related cancers.