Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer, causing ~10,000 annual deaths in the US, similar to the mortality rate of commonly studied cancers such as melanoma, leukemia, lymphoma, and urothelial cancers. Despite its increasing prevalence in an aging population, however, much less is known about high-risk cSCC (i.e. locally advanced or metastatic at presentation). Current therapies for high-risk cSCC are limited by high toxicity and low therapeutic efficacy. Chronic wounds, repetitive injury and burns are major risk factors for high-risk cSCCs, suggesting an oncogenic process that co-opts an abnormal ...

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Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer, causing ~10,000 annual deaths in the US, similar to the mortality rate of commonly studied cancers such as melanoma, leukemia, lymphoma, and urothelial cancers. Despite its increasing prevalence in an aging population, however, much less is known about high-risk cSCC (i.e., locally advanced or metastatic at presentation). Current therapies for high-risk cSCC are limited by high toxicity and low therapeutic efficacy. Chronic wounds, repetitive injury, and burns are major risk factors for high-risk cSCCs, suggesting an oncogenic process that co-opts an abnormal wound healing response. I identified a novel, innate immune-like pathway that senses and regulates skin wound repair and is significantly upregulated in nearly all human cancers. While the innate immune system is essential for host pathogen defense, my studies and others provide increasing evidence for a role of innate immunity in cancer surveillance. Exploiting my expertise in studying skin wound repair and innate immunity, I will characterize how cancer hijacks or alters innate immune signaling during normal physiological repair. I will focus on the following studies to understand the relationship between cancer and epithelial tissue repair using skin as an initial model: Aim 1) the locoregional role of innate immunity in repairing epithelial damage and fueling cancer growth; Aim 2) the role of innate immunity in clearance of wound-induced malignancy; and Aim 3) understanding how local insults leads to systemic responses such as cancer cachexia. The results will provide insight into cellular pathways that promote high-risk cSCC in chronic wounds and lead to novel, targeted therapeutic strategies against wound-induced cSCC. They will generate preliminary results as the basis for future research grants and new research directions that exploit innate immunotherapy.

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