Non-melanoma skin cancer: new and future synthetic drug treatments

ABSTRACT

Introduction: Non-melanoma skin cancers (NMSC) mainly comprise two different entities: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC); beneath these two entities, Merkel cell carcinoma, adnexal tumors, dermatofibrosarcoma protuberans, angiosarcoma, and cutaneous lymphoma belong to NMSC. These rare skin tumors are not the topic of this review.

BCC and SCC are the most common cancers diagnosed in humans. The preferred treatment is surgery, which in most cases is curative. Although a high recurrence rate is seen, these cancers rarely metastasize. Therefore, systemic treatments were not a priority for these patients. It is long known that the abnormal activation of Hedgehog and epidermal growth factor receptor pathways were involved in BCC and SCC. In the last decade, metastatic disease became an important area of research, mostly because new therapies that targeted components of these two pathways became available.

Areas covered: Here we cover the available therapeutic options for patients diagnosed with BCC and SCC, focus on systemic and targeted therapies.

Expert opinion: BCC and SCC are common cancers, with good prognosis. More than the metastatic disease, advanced local disease and recurrent disease pose clinicians a great challenge. Albeit there are promising results with targeted therapies, resistance development has already been described.

KEYWORDS:

• Non-melanoma skin cancer
• keratinocyte cancers
• BCC
• SCC
• medical treatment

Article Highlights

• NMSC mainly comprise two different entities, BCC and SCC, which are the most frequently diagnosed cancers.

• The preferred treatment is surgery. However, for patients in whom this is not possible, systemic therapy is available.

• Mutations involving the Hedgehog pathway components play an important role in BCC carcinogenesis and drugs targeting these mutations are now available.

• Dysregulation of the epidermal growth factor receptor pathway is involved in SCC pathogenesis. In metastatic disease treatment, EGFR inhibitors can be used alone or in combination with chemotherapy and/or radiotherapy.

• The promising results with immune checkpoint inhibitors even in heavily pre-treated patients make room for more investigation on this field. Probably, these compounds will be part of the future therapeutic options for NMSC.

This box summarizes key points contained in the article.

Declaration of interest

T Amaral reports grants from Roche, grants from Bristol-Myers Squib, grants from Merck Sharp & Dohme, outside the submitted work. C Garbe reports grants and personal fees from Novartis, grants and personal fees from Roche, during the conduct of the study; personal fees from Amgen, grants and personal fees from Bristol-Myers Squibb, personal fees from Merck Sharp & Dohme, personal fees from Philogen, outside the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded