Hereditary diffuse gastric cancer therapeutic roadmap: current and novel approaches in a nutshell

Therapeutic Advances in Medical Oncology
Fadi E El RamiGebran W Khneizer

Abstract

Hereditary diffuse gastric cancer (HDGC) is a rare malignancy characterized by autosomal dominant inheritance of pathological variants of the CDH1 gene encoding E-cadherin, which is involved in cell-cell adhesion, maintenance of epithelial architecture, tumor suppression, and regulation of intracellular signaling pathways. Late-stage recognition of HDGC is typically associated with a poor clinical outcome due to its metastatic potential and risk of lobular breast cancer (LBC) development. The American College of Gastroenterology issued guidelines to evaluate HDGC, test for CDH1 genetic variants, and recommend prophylactic gastrectomy for carriers of CDH1 mutations. If surgery is not pursued, endoscopy is a surveillance alternative, although it carries a limited ability to detect malignant foci. As part of clinical research efforts, novel endoscopy advances are currently studied, and a center of excellence for HDGC was created for a comprehensive multidisciplinary team approach. Within this review, we cover current conventional treatment modalities such as gastrectomy and chemotherapy, as the mainstay treatments, in addition to Pembrolizumab, an immune checkpoint inhibitor, as the last therapeutic resort. We also shed light on n...Continue Reading

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Methods Mentioned

BETA
biopsies
biopsy
glycosylation
surgical resection

Clinical Trials Mentioned

NCT03648879
NCT03030404
NCT04253106
NCT00582257
NCT00633607
NCT03950908
NCT00548548
NCT03421288
NCT03472365
NCT02340975

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