Chronic inflammation is a highly prevalent consequence of changes in environmental and lifestyle factors that contribute to the development of cancer. The basis for this critical association has largely remained unclear. The MUC1 gene evolved in mammals to protect epithelia from the external environment. The MUC1-C subunit promotes responses found in wound healing and cancer.
MUC1-C appeared in mammals to protect epithelia from inflammation and loss of homeostasis. MUC1-C activates a wound healing response that has been misappropriated by cancer cells which, in addition to loss of polarity, includes induction of proliferation, EMT and epigenetic reprogramming. MUC1-C also induces chromatin remodeling, dedifferentiation and pluripotency factor expression. Activation of these responses, if sustained as in chronic inflammation, can result in a stable or irreversible reprogramming of the epigenome that promotes cancer progression and, in turn, drug resistance and immune evasion.
Given this capacity, MUC1-C has emerged as an important target for the development of vaccines, CAR-T cells, ADCs, bispecific antibodies and small molecule inhibitors, among other therapeutic approaches.
To support research at Kufe Lab or donate to other areas of the Dana-Farber Cancer Institute, please contact the Philanthropy office: 617-632-6099 or complete a gift form using the ‘Give Now’ link.