Targeting MUC16 in Cancer Therapy

Abstract

Over the recent decades, there has been a number of studies investigating the role of mucins in the pathogenesis of various cancers such as breast, lung, ovarian, gastrointestinal and pancreatic malignancies. Since then, it has been discovered that mucins play a critical role in tumorigenesis as they can mediate cell proliferation, metastasis and resistance to chemotherapy. Thus, mucins have been explored as a potential therapeutic target as well as a biomarker, as cancer cells often have an aberrant expression of mucins. MUC16 is a glycoprotein coded by one of the 21 mucin genes. CA125, the extracellular domain of MUC16, is a well-established biomarker for ovarian cancer, however there is no in depth literature review on MUC16 as a target for anti-cancer therapy. Thus, this review summarises the existing literature on MUC16, the current therapies targeting on MUC16 and highlights future avenues for targeting mucin-producing cancers.

Optimization of an oral mucosa in vitro model based on cell line TR146

“…55 To our best knowledge, the presence of MUC6 has not been shown in the oral mucosa until now, whereby the expression of MUC16 in saliva samples of healthy patients and patients with oral squamous carcinoma showed no correlation to the prognosis as described by Suh et al (2017). 56 On the other hand, all samples expressed MUC1A, MUC1B, MUC3A, MUC15, MUC18, and MUC20. The expression of MUC1 in the buccal area and salivary glands has been described before.…”

Association of MUC16 Mutation With Tumor Mutation Load and Outcomes in Patients With Gastric Cancer

“…14 Nonetheless, MUC16 is known to modulate immune response to cancer. 6 Our gene set enrichment analyses also indicated that immune response, cell cycle checkpoints, and DNA replication and repair were significantly altered in GC samples with MUC16 mutations. Therefore, therapeutic regimens to abrogate immune inhibition, such as immune checkpoint blockade, may be beneficial for patients with GC who have MUC16 mutations.…”

“…5 MUC16 is a type I transmembrane mucin protein with 3 components: a C-terminal domain, a tandem repeat region, and an extracellular N-terminal section. 6,7 Cancer antigen 125 (CA-125), used to monitor disease progression in ovarian cancer, is part of the tandem repeat domain. 7 MUC16 (OMIM 606154) is one of the most frequently mutated genes in GC; however, its associations with TML and prognosis remainunclear.Inthisstudy,weinvestigatedwhetherMUC16mutations are associated with TML and prognosis in patients with GC.…”

A Mucin 16 bispecific T cell–engaging antibody for the treatment of ovarian cancer

“…Because of the potency of a bispecific antibody, it is essential to identify a tumor target antigen with sufficient tumor selectivity to limit toxicity. Mucin 16 (MUC16) is a large integral membrane glycoprotein that is highly expressed in a number of epithelial cancers (16) but at low abundance in epithelial cells of several tissues including trachea, eye, and female reproductive organs, as well as the serosal epithelial lining of the peritoneal and thoracic cavity. MUC16 is thought to provide a barrier function in some of these organs (17,18).…”