New study shows promise for preventing therapy resistance in tumor cells

January 9, 2014 by Allison Perry, University of Kentucky

A new study led by University of Kentucky researchers suggests that activating the tumor suppressor p53 in normal cells causes them to secrete Par-4, another potent tumor suppressor protein that induces cell death in cancer cells. This finding may help researchers decipher how to inhibit the growth of tumors that have become resistant to other treatments.

Loss of the often contributes to therapy resistance in tumors. In the study, published in Cell Reports, the University of Kentucky's Vivek Rangnekar and his colleagues activated wild type p53 in to trigger cell death in the p53-deficient cancer cells. Because p53 is intact and functional in normal cells, the researchers harnessed its potential to inhibit the growth of p53-deficient cancer cells.

This paracrine effect was brought about by the tumor suppressor Par-4, which specifically kills cancer cells. Although other tumor suppressors exist, what makes Par-4 so special is that it is not mutated as frequently as other known suppressors, and it's "selective" in its actions in that Par-4 will only kill cancer cells and not normal cells. Importantly, it's secretion from normal cells can be induced by activating p53 so that Par-4 enters circulation, thereby potentially targeting at distant sites.

"As normal cells far outnumber the cancer cells in patients, we sought to empower the normal cells to trigger in p53-deficient ," said Rangnekar, associate director of transdisciplinary collaborations for the UK Markey Cancer Center. "Our findings have potential for targeting local, as well as metastatic tumors, and future studies will use FDA-approved drugs to induce Par-4 secretion."

Explore further: UK's "super mouse" yielding major discoveries in cancer research

Related Stories

UK's "super mouse" yielding major discoveries in cancer research

July 26, 2013
It appears tiny and inconsequential enough, but the "super mouse"—created by researchers at the University of Kentucky Markey Cancer Center some six years ago—has spawned plenty of new research into preventing and/or ...

Tipping the balance between senescence and proliferation

November 15, 2013
An arrest in cell proliferation, also referred to as cellular senescence, occurs as a natural result of aging and in response to cellular stress. Senescent cells accumulate with age and are associated with many aging phenotypes, ...

Biologists ID new cancer weakness

November 14, 2013
About half of all cancer patients have a mutation in a gene called p53, which allows tumors to survive and continue growing even after chemotherapy severely damages their DNA.

Bone marrow transplantation may increase cancer resistance in patients

August 24, 2011
Bone marrow transplantation with genetically modified cells may prolong the period of cancer-free survival, suggests a study led by Dr. Vivek Rangnekar, associate director of translational research for the Markey Cancer Center ...

Researchers discover a tumor suppressor gene in a very aggressive lung cancer

January 9, 2014
The Genes and Cancer Group at the Cancer Epigenetics and Biology Program of the IDIBELL has found that the MAX gene, which encodes a partner of the MYC oncogene, is genetically inactivated in small cell lung cancer. Reconstitution ...

Drug kills cancer cells by restoring faulty tumor suppressor

May 14, 2012
A new study describes a compound that selectively kills cancer cells by restoring the structure and function of one of the most commonly mutated proteins in human cancer, the "tumor suppressor" p53. The research, published ...

Recommended for you

More than 2,500 cancer cases a week could be avoided

March 23, 2018
More than 135,500 cases of cancer a year in the UK could be prevented through lifestyle changes, according to new figures from a Cancer Research UK landmark study published today.

Metastatic lymph nodes can be the source of distant metastases in mouse models of cancer

March 22, 2018
A study by Massachusetts General Hospital (MGH) investigators finds that, in mouse models, cancer cells from metastatic lymph nodes can escape into the circulation by invading nodal blood vessels, leading to the development ...

Could a pap test spot more than just cervical cancer?

March 22, 2018
Pap tests have helped drive down rates of cervical cancer, and a new study suggests they also could be used to detect other gynecologic cancers early.

Researchers identify compound to prevent breast cancer cells from activating in brain

March 22, 2018
Researchers at Houston Methodist used computer modeling to find an existing investigational drug compound for leukemia patients to treat triple negative breast cancer once it spreads to the brain.

Researchers examine role of fluid flow in ovarian cancer progression

March 22, 2018
New research from Virginia Tech is moving physicians closer to pinpointing a predictor of ovarian cancer, which could lead to earlier diagnosis of what is know as the "silent killer."

Probing RNA epigenetics and chromatin structures to predict drug resistance in leukemia

March 22, 2018
Drug resistance is a major obstacle to effective treatment for patients with cancer and leukemia. Epigenetic modifying drugs have been proven effective for some patients with hematologic malignancies, such as myelodysplastic ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.