Yale Researchers Discover New Cancer Cell Vulnerability

Researchers Discover New Cancer Cell Vulnerability

Chromosomes (in blue) and their telomores (in red). Credit: Narenda Wajepeyee, Yale School of Medicine

New research from Yale University found that simultaneous inhibition of both telomerase and p21 inhibited tumor growth in mice.

Yale School of Medicine and Yale Cancer Center researchers have uncovered a genetic vulnerability of cancer cells that express telomerase — an enzyme that drives their unchecked growth — and showed that telomerase-expressing cells depend upon a gene named p21 for their survival.

The authors found that simultaneous inhibition of both telomerase and p21 inhibited tumor growth in mice. The telomerase enzyme is overexpressed in over 90% of human cancers, but not in normal cells, and expression of telomerase is necessary to initiate and promote cancer growth. In this study, the Yale team, led by first author Romi Gupta and corresponding author Narendra Wajapeyee of the Department of Pathology, showed how new pharmacological drug combinations can be applied to simultaneously target both telomerase and p21 to induce cell death in telomerase-expressing cancer cells.

Finally, the authors also showed that their approach is also applicable for p53 mutant cancers if telomerase and p21 inhibition are combined with pharmacological restoration of p53 tumor suppressor activity. The study, which could open doors to novel therapies for telomerase inhibition, appears in the Proceedings of the National Academy of Sciences.

Reference: “Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A” by Romi Gupta, Yuying Dong, Peter D. Solomon, Hiromi I. Wettersten, Christopher J. Cheng, JIn-Na Min, Jeremy Henson, Shaillay Kumar Dogra, Sung H. Hwang, Bruce D. Hammock, Lihua J. Zhu, Roger R. Reddel, W. Mark Saltzman, Robert H. Weiss, Sandy Chang, Michael R. Green and Narendra Wajapeyee, 14 July 2014, PNAS.
DOI:  10.1073/pnas.1411370111


1 Comment on "Yale Researchers Discover New Cancer Cell Vulnerability"

  1. Madanagopal.V.C. | July 22, 2014 at 5:00 am | Reply

    Telomerase is the tool for longevity and its gradual tapering down over millions of copies,in cell replication ,the cells should suffer a death. This is nothing but a programmed cell death which is very very essential in the embryonic stage and also in scars healing apart from the basic function of telomeres to stunt the growth in evolution slowly moulding the morphology according to the environment and available food. This basic plan would go haywire if induced by some chemicals carcinogenic or radiation,and thereby the telomerase gets produced rapidly increasing unwanted growth in tumours. So it is a right plan to inhibit the production of telomerase apart from killing the cancerous cells by chemo therapy. Thank You.

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