329 Mechanisms of Cutaneous Adverse Events during Targeted Cancer Therapy

Aberrant activation of EGFR is seen in many solid cancers, which has led to the development EGFR-targeted anti-cancer therapies. However, epidermal growth factor receptor (EGFR) plays an important role hair morphogenesis and maintenance skin homeostasis. Therefore, cancer patients receiving inhibitors commonly develop a papulopustular rash, pruritus dry skin. Severe adverse events may require interruption otherwise effective therapy. Mice with genetic ablation cells inflammation closely mimics hallmarks inhibition humans. Using this mouse model inhibitor-induced we could recently show that barrier defect are initiated during de-novo eruption accompanied by type 2 cytokines. This dysfunction be rescued SOS, lies upstream Ras-Raf-MEK-ERK pathway, thus implying similar mechanism behind cutaneous induced MEK others targeting signaling hub. models deletion different compartments follicle, identified activity especially crucial upper follicle. We now further aim unfold how controlling immunological quiescence follicular integrity eruption. To discover cellular molecular key players, creating single-cell transcriptomic atlas EGFR-deficient epidermis shaft emergence. Ultimately, study aims druggable pathways responsible for initiation associated targeted therapy facilitate supporting care treatment patients.