Ptch1, short for Patched 1, is a tumor suppressor and serves as the receptor of Hedgehog (HH) ligand, negatively regulating the HH signaling pathway [2]. This pathway is crucial in various biological processes such as embryonic development, cell proliferation, and tissue homeostasis. Mutations in Ptch1 are implicated in many human cancers, highlighting its importance in maintaining normal cellular function [2]. Genetic models, like gene knockout (KO) and conditional knockout (CKO) mouse models, can be valuable in studying Ptch1.

In Keratocystic odontogenic tumors (KCOTs), a high frequency (93%) of Ptch1 inactivating mutations was identified in sporadic cases, with biallelic inactivation in 80% of cases, indicating SHH pathway alterations are nearly universal in these neoplasms [4]. In non-small cell lung cancer (NSCLC), knockdown of Ptch1 inhibited spherical colony formation, migration, and invasion of NSCLC cells, as well as decreased bone destruction and osteoclastogenesis in a mouse bone metastasis model, suggesting Ptch1 promotes anchorage-independent growth and bone invasion [1]. In colorectal and gastrointestinal cancers, Ptch1 mutations were associated with higher durable clinical benefit rates, progression-free survival, overall survival, and increased antitumor immune signatures, making Ptch1 mutation a potential biomarker for predicting response to immunotherapy [3,5].

In conclusion, Ptch1 plays an essential role in regulating the HH signaling pathway, which is fundamental for normal development and cellular function. Studies using KO/CKO mouse models and other loss-of-function experiments have revealed its significance in cancer-related processes, including tumor growth, metastasis, and response to immunotherapy. These findings offer potential avenues for therapeutic interventions targeting Ptch1-related diseases.