Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer

Version 1 : Received: 12 September 2022 / Approved: 14 September 2022 / Online: 14 September 2022 (09:23:16 CEST)

A peer-reviewed article of this Preprint also exists.

Nicheperovich, A.; Townsend-Nicholson, A. Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer. J. Pers. Med. 2022, 12, 1648. Nicheperovich, A.; Townsend-Nicholson, A. Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer. J. Pers. Med. 2022, 12, 1648.

Abstract

The G protein-coupled receptor (GPCR) Smoothened (Smo) is a central signal transducer of the Hedgehog (Hh) pathway which has been linked to diverse forms of tumours. Stimulated by advancements in structural and functional characterisation, the Smo receptor has been recognised as an important therapeutic target in Hh-driven cancers, and several Smo inhibitors have now been approved for cancer therapy. This receptor is also known to be an oncoprotein itself and its gain-of-function variants have been associated with skin, brain, and liver cancers. According to the COSMIC database, oncogenic mutations of Smo have been identified in various other tumours, although their oncogenic effect remains unknown in these tissues. Drug resistance is a common challenge in cancer therapies targeting Smo, and data analysis shows that healthy individuals also harbour resistance mutations. Based on the importance of Smo in cancer progression and the high incidence of resistance towards Smo inhibitors, this review suggests that detection of Smo variants through tumour profiling could lead to increased precision and improved outcomes of anti-cancer treatments.

Keywords

Smoothened; cancer; precision medicine; therapy

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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