Understanding the unique attributes of muc16 (ca125): potential implications in targeted therapy

Srustidhar Das, Surinder K. Batra

Research output: Contribution to journalReview article

36 Scopus citations

Abstract

CA125, the most widely used ovarian cancer biomarker, was first identified approximately 35 years ago in an antibody screen against ovarian cancer antigen. Two decades later, it was cloned and characterized to be a transmembrane mucin, MUC16. Since then, several studies have investigated its expression, functional, and mechanistic involvement in multiple cancer types. Antibodybased therapeutic approaches primarily using antibodies against the tandem repeat domains of MUC16 (e.g., oregovomab and abagovomab) have been the modus operandi for MUC16-targeted therapy, but have met with very limited success. In addition, efforts have been also made to disrupt the functional cooperation of MUC16 and its interacting partners; for example, use of a novel immunoadhesinHN125to interfereMUC16binding to mesothelin. Since the identification of CA125 to be MUC16, it is hypothesized to undergo proteolytic cleavage, a process that is considered to be critical in determining the kinetics of MUC16 shedding as well as generation of a cell-associated carboxyl-terminal fragment with potential oncogenic functions. In addition to our experimental demonstration of MUC16 cleavage, recent studies have demonstrated the functional importance of carboxyl terminal fragments of MUC16 in multiple tumor types. Here, we provide how our understanding of the basic biologic processes involving MUC16 influences our approach toward MUC16-targeted therapy.

Original languageEnglish (US)
Pages (from-to)4669-4674
Number of pages6
JournalCancer Research
Volume75
Issue number22
DOIs
StatePublished - Nov 15 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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