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Epidermal growth factors (EGFs) Market play important roles in the development, homeostasis and repair of various tissues including skin. As the name suggests, EGFs were originally identified as factors involved in stimulating the proliferation of epidermal tissues. However, extensive research over the past few decades has revealed that EGFs have much wider biological functions and deregulation of EGF signalling is linked to various diseases including cancer. This article discusses the functions of EGFs in skin development and repair as well as their role in cancer progression.
Discovery and Functions of EGFs
Epidermal growth factor was one of the first growth factors to be discovered and characterized in the early 1960s. It was found to stimulate the proliferation of epidermal cells and fibroblasts in culture. Since then, several other factors binding to the EGF receptor (EGFR) have been identified and collectively termed as EGF family members. Some key EGF family members involved in skin development and homeostasis include EGF, transforming growth factor alpha (TGF-α), amphiregulin, heparin-binding EGF and betacellulin.
EGF family members play important roles during embryonic development by regulating processes like epithelial-mesenchymal interactions, organogenesis and tissue morphogenesis. In adults, they are involved in continuous self-renewal and repair processes in tissues with high turnover rates such as skin, gastrointestinal tract and lungs. Upon injury, EGFs are rapidly upregulated at the wound site to stimulate proliferation and migration of keratinocytes, fibroblasts and endothelial cells for re-epithelialization and tissue regeneration. EGFs also regulate other functions like differentiation, apoptosis and inflammatory responses during repair.
Role of EGF Signalling in Skin Cancer
Aberrant EGF signalling has been implicated in the development and progression of various cancers including skin cancers. Chronic inflammation and wounding can lead to prolonged EGF stimulation and activation of proliferative pathways, thereby increasing cancer risk over time. Genetic alterations resulting in overexpression of EGF ligands or EGFR are frequently observed in different skin cancers.
Non-melanoma skin cancers (NMSC) which include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) arise from the epidermis or keratinocytes. Altered Hedgehog signalling is the main driver of BCC, however EGFR overexpression and constitutive activation also contribute to BCC development and growth. In SCC, autocrine stimulation of EGFR by overexpressed ligands like TGF-α or amphiregulin leads to increased proliferation and survival of malignant keratinocytes. This hyperactivation of EGF signalling is considered an important factor in SCC pathogenesis.
Melanoma arises from melanocytes and is the deadliest form of skin cancer. While genetic and environmental risk factors like UV exposure play a role, aberrant MITF and MAPK pathway signalling drive melanomagenesis. Cross-talk between these pathways and EGFR signalling enhances melanoma progression and metastasis. Upregulation of various EGF ligands in melanoma tumours can induce an autocrine signalling loop promoting cell growth, survival, migration and invasiveness.
Targeting EGFR Signalling for Cancer Treatment
Given the strong association between EGF signalling and skin cancer, inhibitors targeting different nodes in this pathway have become important anticancer drugs. Monoclonal antibodies against EGFR like cetuximab can block ligand binding and receptor activation. Tyrosine kinase inhibitors (TKIs) like erlotinib specifically target the intracellular kinase domain of EGFR.
These anti-EGFR therapies have shown clinical efficacy against various NMSCs and are now approved for use in SCC and BCC. They may improve responses when combined with conventional chemotherapy, radiation therapy or other targeted agents in advanced stages. In melanoma, anti-EGFR strategies are being evaluated, especially in combination with BRAF/MEK inhibitors in BRAF mutated cancers. Though responses are usually transient, these drugs can improve progression-free survival and quality of life for many patients.
Ongoing research and clinical trials are further exploring use of anti-EGFR drugs in adjuvant and neoadjuvant settings to prevent recurrence or offer organ preservation. Development of resistant mutations on EGFR continues to pose a challenge. New generation inhibitors targeting downstream effectors or combination regimens are being evaluated to improve outcomes. With better understanding of molecular drivers, personalized treatment approaches targeting both EGFR and other cooperating oncogenic pathways hold promise to minimize toxicity and maximize benefits for skin cancer patients.
Conclusion
In summary, EGFs play essential roles in skin development, homeostasis and repair. However, deregulated Epidermal Growth Factors (EGF) Market signalling arising from genetic or epigenetic alterations can drive the pathogenesis of various skin cancers. Anti-EGFR therapies targeting different nodes in this pathway have shown promising clinical efficacy against NMSCs and hold potential in melanoma as well. Continued research on mechanisms of EGFR activation and resistance along with rational combination strategies will be necessary to further improve skin cancer management. A tailored approach targeting both EGFR and other pathways will likely provide maximum therapeutic gains.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
