MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress

Abstract

Over three decades have passed since the first report on the expression of CA125 by ovarian tumors. Since that time our understanding of ovarian cancer biology has changed significantly to the point that these tumors are now classified based on molecular phenotype and not purely on histological attributes. However, CA125 continues to be, with the recent exception of HE4, the only clinically reliable diagnostic marker for ovarian cancer. Many large-scale clinical trials have been conducted or are underway to determine potential use of serum CA125 levels as a screening modality or to distinguish between benign and malignant pelvic masses. CA125 is a peptide epitope of a 3–5 million Da mucin, MUC16. Here we provide an in-depth review of the literature to highlight the importance of CA125 as a prognostic and diagnostic marker for ovarian cancer. We focus on the increasing body of literature describing the biological role of MUC16 in the progression and metastasis of ovarian tumors. Finally, we consider previous and on-going efforts to develop therapeutic approaches to eradicate ovarian tumors by targeting MUC16. Even though CA125 is a crucial marker for ovarian cancer, the exact structural definition of this antigen continues to be elusive. The importance of MUC16/CA125 in the diagnosis, progression and therapy of ovarian cancer warrants the need for in-depth research on the biochemistry and biology of this mucin. A renewed focus on MUC16 is likely to culminate in novel and more efficient strategies for the detection and treatment of ovarian cancer.

Oncogenic KRAS Targets MUC16/CA125 in Pancreatic Ductal Adenocarcinoma

“…CA125 was firstly detected in ovarian cancer and had been reported to be positive in 80% of ovarian epithelial tumor patients (10). In addition, the positive observation of CA125 is also seen in breast cancer, pancreatic cancer, gastric cancer, and some other tumors (11). Carcinoembryonic antigen (CEA) is a nonspecific tumor marker and is commonly used for detection of colorectal cancer (12).…”

Detecting the potential cancer association or metastasis by multi-omics data analysis

“…Previous studies have identified TTN somatic mutations in multiple cancer types including melanoma, glioblastoma and pancreatic carcinoma, suggesting that the cellular functions of these molecules could possibly be related to a common tumor progression mechanism (Balakrishnan et al, 2007). MUC16 performs a number of important biological roles in cancer cell signaling, metastasis, regulation of immune responses and in anti-cancer therapeutic strategies (Felder et al, 2014). Also of note, we observed that CSMD3 harbored more mutations in Luad than in other types of cancer; in fact, 44% of Luad patients were found to have mutations in the CSMD3 region.…”

Targeting MUC16 in Cancer Therapy

“…It is a well-established biomarker used to monitor the progression and recurrence of ovarian cancer. Furthermore, it is overexpressed in a range of human malignancies including ovarian, pancreatic, breast, cholangiocarcinoma, cervical, gastric and non-small cell lung cancer [1][2][3][4][5][6]. Mucins are a family of high molecular weight glycoproteins composed of oligosaccharides attached to a peptide core [7].…”

“…Several hundred oligosaccharides are attached to the N-terminal domain through O-linked glycosylation and N-linked glycosylation whilst the tandem repeat region (TRR) has approximately 60 repeats of a 156 amino acid sequence, with disulphide bonds that confers structural stability. Attached to the TRR is a smaller C-terminal domain that also contains a cytoplasmic tail involved in intracellular cell events ( Figure 1) [1,3,8].…”

“…MUC16 is a type of Type 1 transmembrane mucin with a molecular weight of 3-5 million Da [1], making it the largest glycoprotein out of the mucin family. It is a well-established biomarker used to monitor the progression and recurrence of ovarian cancer.…”