Molecular Basis and Rationale for the Use of Targeted Agents and Immunotherapy in Sinonasal Cancers

Abstract

Despite the progress of surgery, radiotherapy, and neoadjuvant chemotherapy, the prognosis for advanced sinonasal cancers (SNCs) remains poor. In the era of precision medicine, more research has been conducted on the molecular pathways and recurrent mutations of SNCs, with the aim of understanding carcinogenesis, helping with diagnosis, identifying prognostic factors, and finding potentially targetable mutations. In the treatment of SNC, immunotherapy is rarely used, and no targeted therapies have been approved, partly because these tumors are usually excluded from major clinical trials. Data on the efficacy of targeted agents and immune checkpoint inhibitors are scarce. Despite those issues, a tumor-agnostic treatment approach based on targeted drugs against a detected genetic mutation is growing in several settings and cancer subtypes, and could also be proposed for SNCs. Our work aims to provide an overview of the main molecular pathways altered in the different epithelial subtypes of sinonasal and skull base tumors, focusing on the possible actionable mutations for which potential target therapies are already approved in other cancer types.

Progress and emerging strategies to preserve function in the treatment of sinonasal cancer

“…Genetic analysis also allows for the identification of molecular targets for modern targeted therapies. Next‐generation sequencing identified recurrent subtype‐unique mutations likely to be considered molecular targets: APC, CTNNB1, PIK3CA, and KRAS in intestinal‐type adenocarcinomas, EGFR and CDKN2A in SCC, NRAS and NF1 in mucosal melanomas, IDH2 in SNUC, and ARID1A, SMARCB1 and SMARCA4 in neuroendocrine and SNUC 48 . Other markers such as Somatostatin receptor 2 (SSTR2) expression were also reported in sinonasal cancers, such as in ONB 54 .…”

“…The promise of biologic response modifiers that enhance an immune response against selected head and neck cancers presents novel alternative strategies for preservation of function. While such protocols for SNC remain investigational, there is preliminary evidence that such tumors are sensitive to these agents 48 …”

“…While such protocols for SNC remain investigational, there is preliminary evidence that such tumors are sensitive to these agents. 48 The pathogenesis of most sinonasal malignancies is currently poorly understood, mainly due to their rarity. Both abnormal cell proliferation and programmed cell death imbalance appear to drive the malignant transformation of precursor lesions.…”

Ligation of the ethmoid arteries in superselective intra‐arterial infusion of cisplatin for advanced maxillary sinus cancer fed by the ophthalmic artery

“…The discovery of biomarkers like genetic abnormalities and epigenetic variations in various cancer types has been made possible by recent developments in molecular biological research. Gene expression analysis is utilized to develop and clinically use innovative treatment agents, such as targeted therapies and immune checkpoint inhibitors, and to uncover prognostic markers in head and neck cancer 17,18 . Precision medicine with molecularly targeted drugs and immune checkpoint inhibitors is also expected in advanced nasal sinus cancer.…”

“…Gene expression analysis is utilized to develop and clinically use innovative treatment agents, such as targeted therapies and immune checkpoint inhibitors, and to uncover prognostic markers in head and neck cancer. 17,18 Precision medicine with molecularly targeted drugs and immune checkpoint inhibitors is also expected in advanced nasal sinus cancer.…”