Targeting receptor tyrosine kinase signaling - Avenues in the management of cutaneous squamous cell carcinoma

Q: What role does RTK signaling play in cutaneous squamous cell carcinoma (cSCC)?

RTK signaling triggers key events that contribute to the development and progression of cSCC. The review emphasizes RTKs as major contributors and therapeutic targets.

Q: How are receptor tyrosine kinases activated according to the article?

RTKs are activated when ligands bind to specific receptors, promoting receptor dimerization/oligomerization. This conformational change enables phosphorylation of tyrosine kinase domains and downstream signaling through SH2/PTB-containing proteins.

Q: What does the review say about targeting RTKs in cSCC?

RTK inhibition has produced favorable results, but therapeutic outcomes still need improvement. The review discusses clinical trial observations and preclinical insights, including natural products that may suppress RTK signaling and skin carcinogenesis.

Sep 24, 2026

Uploaded by River Wang

Non-melanoma skin cancer is a leading global diagnosis, and cutaneous squamous cell carcinoma (cSCC) represents an aggressive and common subtype. This review explains how receptor tyrosine kinase (RTK) signaling drives cSCC progression and how RTK inhibition has shown therapeutic benefits yet leaves room for improved outcomes. It summarizes evidence from clinical trials and preclinical work, including approaches using natural products to suppress RTK signaling and skin carcinogenesis.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Summary

Introduction

Receptor Tyrosine Kinase Signaling

EGFR

iScience ll OPEN ACCESS Review Targeting receptor tyrosine kinase signaling: Avenues in the management of cutaneous squamous cell carcinoma Mohan Shankar Gopinatha Pillai, 1,2 Sreekumar U. Aiswarya, 1 Chenicheri K. Keerthana, 1 Tennyson P. Rayginia,1 and Ruby John Anto 1,3,* SUMMARY Non-melanoma skin cancer (NMSC) is the most frequently diagnosed cancer worldwide. Among the various types of NMSCs, cutaneous squamous cell carcinoma (cSCC) exhibits more aggressive phenotype and is also the second-most prevalent type. Receptor tyrosine kinases (RTK) triggers key signaling events that play critical roles in the development of various cancers including cSCC. Unsurprisingly, for this reason, this family of proteins has become the cynosure of anti-cancer drug discovery pipelines and is also being considered as attractive targets against cSCC. Though inhibition of RTKs in cSCC has yielded favourable results, there is still scope for bettering the therapeutic outcome. In this review, we discuss the relevance of RTK signaling in the progression of cutaneous squamous cell carcinoma, and observations from clinical trials that used RTK inhibitors against cSCC. Backed by results from preclinical studies, including those from our lab, we also give insights into the scope of using some natural products as effective suppressors of RTK signaling and skin carcinogenesis. INTRODUCTION Non-melanoma skin cancer (NMSC) is the most frequently diagnosed cancer worldwide with the highest incidence rate reported in Australia (>1000/100,000 persons) and the lowest in Africa (<1/100,000 persons) .1 Among NMSCs, basal cell carcinoma is the most prevalent form constituting 75% of the total NMSC cases followed by cutaneous squamous cell carcinoma (cSCC), which constitutes the huge majority of the rest of NMSC incidences.2 The metastasis rate of NMSC is generally very low with cSCC showing the highest rate of about 3 . 7% of the total cases.3 Major factors that contribute to cSCC are ultraviolet (UV) rays, ionizing radiation, and chemical carcinogens. UVinduced development of intraepithelial lesions, calledﬁeld cancerization, is the precursor ofa major proportion of cutaneous SCCs. These lesions consequently progress to actinic keratosis (AK), which shares similarity with ﬁeldcancerization in exhibiting hyperchromatic and polymorphic nuclei with change in the nucleus to cytoplasmic ratio, and cell polarity.4 However, AK shows unique properties like hyperkeratosis that often contain parakeratotic areas and lymphocytic inﬁltrate that might have implications in disease prognosis. Approximately 65% of cSCCs arise from these precancerous lesions.5 The observed rate of transition of AK lesions into cutaneous squamous cell carcinoma is between0.025%and16%;however, it isnot possible to identify the AK lesions that may progress into cSCC.6,7 Studies focusing on the molecular mechanism of cSCC development have discovered the involvement of oncogenic pathways like Wnt/b-catenin, Notch, and receptor tyrosine kinase (RTK) signaling. RTK signaling has been shown to be a major contributor of cSCC development and is being targeted to treat cSCC. RECEPTOR TYROSINE KINASE SIGNALING Receptor tyrosine kinases comprise an extracellular domain, a transmembrane region, and an intracellular component which consist of a regulatory region, a tyrosine kinase domain and a carboxyl terminal tail. RTKs are activated by binding of ligands to speciﬁc receptors, leading to receptor dimerization/oligomerization. The alteration in their conformation facilitates phosphorylation and activation of tyrosine kinase domains.8 Phosphorylation of RTKs triggers the activation of SH2 or PTB-domain containing proteins which binds to the phosphotyrosine residues of the receptors and propagates downstream signaling. 1Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India 2Present address: Department of surgery, Cedars-Sinai Medical

FAQs

What role does RTK signaling play in cutaneous squamous cell carcinoma (cSCC)?

RTK signaling triggers key events that contribute to the development and progression of cSCC. The review emphasizes RTKs as major contributors and therapeutic targets.

How are receptor tyrosine kinases activated according to the article?

RTKs are activated when ligands bind to specific receptors, promoting receptor dimerization/oligomerization. This conformational change enables phosphorylation of tyrosine kinase domains and downstream signaling through SH2/PTB-containing proteins.

What does the review say about targeting RTKs in cSCC?

RTK inhibition has produced favorable results, but therapeutic outcomes still need improvement. The review discusses clinical trial observations and preclinical insights, including natural products that may suppress RTK signaling and skin carcinogenesis.

Sep 24, 2026

Uploaded by River Wang