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Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities
Stefano Sol1, Fabiana Boncimino1, Kristina Todorova1
1Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Abstract:
Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide. Skin exposure is the leading risk factor for initiating NMSC. Ultraviolet (UV) light induces various genomic aberrations in both tumor-promoting and tumor-suppressing genes in epidermal cells. In conjunction with interactions with a changed stromal microenvironment and local immune suppression, these aberrations contribute to the occurrence and expansion of cancerous lesions. Surgical excision is still the most common treatment for these lesions; however, locally advanced or metastatic disease significantly increases the chances of morbidity or death. In recent years, numerous pharmacological targets were found through extensive research on the pathogenic mechanisms of NMSCs, leading to the development of novel treatments including Hedgehog pathway inhibitors for advanced and metastatic basal cell carcinoma (BCC) and PD-1/PD-L1 inhibitors for locally advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC). Despite the efficacy of these new drugs, drug resistance and tolerability issues often arise with long-term treatment. Ongoing studies aim to identify alternative strategies with reduced adverse effects and increased tolerability. This review summarizes the current and emerging therapies used to treat NMSC.
Insights
Non-melanoma skin cancers (NMSCs) are common globally, driven by UV exposure. New targeted therapies show promise but face resistance and tolerability issues, prompting research into alternatives.
Area of Science:
- Dermatology
- Oncology
- Molecular Biology
Background:
- Non-melanoma skin cancers (NMSCs) are the most common worldwide neoplasms, primarily caused by ultraviolet (UV) radiation.
- UV exposure induces genomic damage in epidermal cells, promoting cancer development alongside stromal and immune system changes.
- While surgical excision is standard, advanced or metastatic NMSCs carry significant morbidity and mortality risks.
Purpose of the Study:
- To review current and emerging therapeutic strategies for non-melanoma skin cancers (NMSCs).
- To highlight advancements in pharmacological targets and novel treatments for NMSC.
- To discuss challenges associated with existing therapies, such as drug resistance and tolerability.
Main Methods:
- Literature review of current and emerging NMSC treatments.
- Analysis of pathogenic mechanisms driving NMSC development.
- Evaluation of novel pharmacological targets and their clinical applications.
Main Results:
- Hedgehog pathway inhibitors are effective for advanced basal cell carcinoma (BCC).
- PD-1/PD-L1 inhibitors show efficacy in advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC).
- Current novel treatments face challenges including drug resistance and tolerability issues.
Conclusions:
- Novel targeted therapies have improved NMSC treatment outcomes.
- Drug resistance and tolerability remain significant challenges in long-term NMSC management.
- Ongoing research focuses on developing alternative, more tolerable NMSC therapies with reduced adverse effects.
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