A Repurposed Small Molecule to Treat Cutaneous Squamous Cell Carcinoma
2022 Harrington Scholar-Innovator
Cutaneous squamous cell carcinoma (cSCC) affects approximately 660,000 individuals in the US annually. Caused by exposure to ultraviolet radiation from sunlight or tanning beds, abnormal skin cells grow at an uncontrollable rate. Identification of a cSCC oncogene target, RET (REarranged during Transfection) and understanding of its downregulation, places early intervention within reach.
“While improved treatment options for metastasized skin cancer are needed, catching cancer in the early stages is even more critical,” says Dr. Carolyn Lee, a physician- scientist and dermatologist who conducts keratinocyte carcinoma screening and treatment at the Veterans Affairs Palo Alto Health Care System.
RET signaling is essential to normal development and maturation of many tissues, but deregulation of its activity contributes to tumor growth in multiple cancers including cSCC. One approach to preventing cSCC is treating precursor lesions, or actinic keratoses (AK), which affect 50 million Americans yearly. Dr. Lee and her team are working toward an effective topical RET inhibitor, which they envision will provide therapeutic cSCC prevention in at-risk persons, such as those with AK.
“Our data indicate RET is activated early in the progression of normal skin to cSCC, and we plan to reverse this action with a topical RET inhibitor that stimulates immature cancer cells to evolve into mature non-dividing forms,” she explains.
The approach has been successful with other cancers, including acute promyelocytic leukemia.
“With Harrington's support, we aim to reduce the incidence of skin cancer with a topical medication option that will be well-tolerated by many, but particularly our military veterans who have sacrificed so much,” Dr. Lee added.