Toronto, ON – Researchers at Mount Sinai Hospital and the University of Toronto have for the first time identified a key common biomarker in breast, prostate, head and neck, and colon cancers. This groundbreaking discovery, which will be published today by Public Library of Science One, reports on a novel common mechanism for the enzymatic degradation of a protein in the cell membrane which leads to the development of cancer in 10 different human epithelial cancers.
“This study demonstrates for the first time that this key biomarker can potentially be used for diagnostic and therapeutic strategies,” said endocrinologist Dr Paul Walfish, Alex and Simona Shnaider research chair in thyroid oncology at Mount Sinai Hospital, professor emeritus at the University of Toronto, and the senior author of the study. “By having a better understanding of how these cancers start and how they will progress, my hope is we will one day be able to create individualize treatment plans and improve outcomes for patients.”
In a recent study published in BMC Cancer, Dr Walfish’s laboratory demonstrated that the nuclear and cytoplasmic accumulation of a novel intracellular domain biomarker called epithelial adhesion molecule intracellular domain (Ep-ICD) was accompanied by a variable reciprocal reduction of its extracellular domain (Ep-Ex) in aggressive thyroid cancers. The current study was designed to determine whether a similar accumulation of Ep-ICD is common in other epithelial cancers.
Researchers analyzed surgical tissues from 10 epithelial cancers, other than thyroid, for their expression of Ep-ICD intracellularly. They found increased nuclear and cytoplasmic Ep-ICD expression and a reduction of Ep-Ex in most of these cancers, most notably in 82% of breast and prostate cancers, 65% of head and neck and colon cancers, and 35% of esophageal tissues. In general, increased intracellular and cytoplasmic expression of Ep-ICD occurred in almost all epithelial cancers analyzed and distinguished them from normal tissues with high sensitivity and specificity with a concomitant variable reduction in membrane Ep-Ex expression in a subset of all cancers.
“By finding a similar biomarker profile in these other cancers, it could account for the ineffectiveness of clinical trials using an monoclonal antibody directed against Ep-Ex in many of these epithelial cancers and lead us to recommend a different treatment path for them,” said Dr Ranju Ralhan, co-director of the Alex and Simona Shnaider Research Laboratory in Molecular Oncology, senior scientist and professor of Department of Otolaryngology-Head & Neck Surgery, and lead author of the study. “The detection of Ep-ICD in a large spectrum of epithelial cancers may explain the limited efficacy reported in Phase III clinical trials which have used targeted monoclonal antibody therapy directed towards the membranous Ep-Ex site rather than the Ep-ICD.”
Future targeted therapies may require analysis of clinical tumour tissue samples for these two EpCAM components to optimize therapy directed towards either Ep-ICD vs. Ep-Ex to improve the treatment of many epithelial cancers.
This research work was supported by grants from the Mount Sinai Hospital Da Vinci Gala Fundraiser, Alex and Simona Shnaider Chair in Thyroid Oncology, the Temmy Latner/ Dynacare Foundation, and the Mount Sinai Hospital Department of Medicine Research Fund and performed in the Shnaider Laboratory in Molecular Oncology in the Department of Pathology and Laboratory at Mount Sinai Hospital, Toronto.
The paper is available online at www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0014130.