New Emerging Treatment Options for Advanced Basal Cell Carcinoma and Squamous Cell Carcinoma

Abstract

Non-melanoma skin cancers, also known as keratinocyte tumors, have an increasing incidence worldwide, with basal cell carcinoma and squamous cell carcinoma being the most represented ones. Although surgery represents the gold-standard treatment for both tumors, some cases can progress to an advanced or a metastatic state and targeted therapy is required. Hedgehog signaling pathway has an important role in the development of basal cell carcinoma, and its inhibition is the key to new treatment options available for the treatment of locally advanced and metastatic basal cell carcinoma. Cutaneous squamous cell carcinoma is the second most frequent malignant skin cancer; when presenting in advanced or metastatic stage, alternative treatments are required; cemiplimab is a human monoclonal antibody directed against programmed cell death-1 receptor that acts by blocking T-cell inactivation and is the first drug approved for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Studies evaluating pembrolizumab, ipilimumab and nivolumab as alternative treatments for advanced squamous cell carcinoma are still underway. Objective of this review is to analyze and discuss the novel therapies for advanced basal cell carcinoma and squamous cell carcinoma to obtain a sharper perspective of the available treatment options.

Dermatologic Disease-Directed Targeted Therapy (D3T2): The Application of Biomarker-Based Precision Medicine for the Personalized Treatment of Skin Conditions—Precision Dermatology

“…Finally, like advanced basal cell carcinomas, advanced cutaneous squamous cell carcinomas may have high mutational burdens, a feature that correlates with response to immunotherapy. The anti-PD1 agent cemiplimab is active in advanced cutaneous squamous cell cancers and is FDA approved for this indication [ 79 , 93 , 94 ].…”

“…Republished from [77] with permission from MDPI (Multidisciplinary Digital Publishing Institute), Barcelona, Spain immunotherapy is also a treatment option for patients with advanced and metastatic BCCs [73,75,76,78]. Currently, cemiplimab-a PD1 inhibitor-is the only FDA-approved immunotherapy agent for Hedgehog inhibitorresistant advanced and metastatic BCCs [74,78,79]. However, there are several reports of other anti-PD1 agents (such as nivolumab or pembrolizumab) that have been successfully used to treat advanced (Figs.…”

Emerging PD-1/PD-L1 targeting immunotherapy in non-small cell lung cancer: Current status and future perspective in Japan, US, EU, and China

“…3 Future perspective PD-1/PD-L1 antibodies are generally approved for NSCLC and can be used in clinical practice in Japan as well as in the US and EU, except for cemiplimab. However, in solid tumors other than NSCLC, pembrolizumab for cervical cancer was approved by the FDA in 2018, cemiplimab and pembrolizumab for cSCC in 2018 and 2020, respectively, and cemiplimab for cBCC in 2021; however, none of these agents were approved for in Japan because Japanese patients were not enrolled in pivotal trials (119)(120)(121). In addition, a number of PD-1/PD-L1 antibodies developed in China have not been approved by the PMDA, FDA, or EMA, which is thought to be due in part to the rise of emerging biopharma companies (EBPs)-those with an estimated expenditure on research and development (R&D) of less than $200 million and less than $500 million in revenuewhich contributed more than 70% of the FDA regulatory submission for approval (122,123).…”

The effect of dermoscopy in assisting on defining surgical margins of basal cell carcinoma

“…Despite BCCs rarely distant metastasizes, some cases may cause severe local aggression including soft tissue, cartilage, and bone. There are various treatment options for BCC including curettage, electrodesiccation, cryosurgery, surgical excision, radiotherapy, photodynamic therapy, and drug therapy with topical chemotherapy, oral, or intralesional injections 2,3 . For the treatment of BCCs, oncological radicality is crucial.…”