Developments in the Treatment of Locally Advanced and Metastatic Squamous Cell Carcinoma of the Skin: A Rising Unmet Need

Abstract

Squamous cell carcinoma of the skin (SCCS) is a common malignancy with potentially devastating consequences in patients with locally advanced or metastatic disease. Its rising incidence, primarily a result of an aging population and increased ultraviolet (UV) radiation exposure, characterize an emerging unmet need. A firm understanding of the biology of this disease, likely distinct from that of other squamous malignancies because of the influence of UV radiation, is necessary in the evaluation of treatment paradigms. Careful recognition of high-risk features pertaining to tumor and host characteristics is paramount to proper management. However, a lack of standardization in guidelines in this regard creates a challenge for physicians. Questions persist regarding additional evaluation and treatment for advanced disease such as the roles for sentinel lymph node biopsy and the adjuvant use of radiation and chemotherapy. With respect to advanced disease, multiple combinations of chemotherapy have been tested with variable success, but no rigorous randomized studies have been conducted. In addition, EGFR inhibitors such as cetuximab and erlotinib have displayed antitumor activity and as such, warrant further investigation. In sum, the treatment of locally advanced and metastatic SCCS is a ripe area for clinical investigation. This article summarizes the current understanding of disease biology and emerging questions in the management of this disease.

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

“…7 Given this rising burden of disease and the limited systemic therapeutic options for advanced cSCC, novel treatment options such as immune checkpoint inhibitors need to be explored. 8 A recent meta-analysis demonstrated that immunohistochemical expression of PD-L1 in tumor cells was associated with clinical response to PD-1/PD-L1 inhibitors in metastatic melanoma and non-squamous NSCLC but not in renal cell carcinoma or squamous NSCLC. Clinical and follow up data:…”

Anti‐programmed cell death‐1 therapy in nonmelanoma skin cancer

“…While there are various treatment options for localized NMSCs, for example surgery, radiotherapy and topical treatment, management of advanced or metastatic NMSCs remains difficult. Single‐agent or combination chemotherapy regimens, as well as antibodies targeting epidermal growth factor receptor, may be used in the treatment of advanced or metastatic SCC . However, the duration of response to the often toxic treatment regimens is limited in most patients.…”

Immunotherapy and squamous cell carcinoma

“…Mutation and hypermethylation can inactivate CDKN2A, which may be responsible for the development of SCC (Figure 1) [5].…”

“…Some studies have reported theincidence of SCC of the skin, in up to 4-31% of those individuals, who were taking Vemurafenib, Dabrafenib and Sorafenib. BRAF-inhibitors may cause mutation in RAS by paradoxical activation of the MAPK pathway ( Figure 1) [5].…”

“…This inactivation of p53 is considered to be a critical step in the development of SCC of the skin. Moreover, TP53 mutations may be responsible for the resistance to chemotherapies (Figure 1) [5,6].…”