New study shows promise for preventing therapy resistance in tumor cells

by Allison Perry

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."

Related Stories

Tipping the balance between senescence and proliferation

Nov 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

Nov 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.

Recommended for you

Endogenous hormones improve breast cancer risk models

15 hours ago

(HealthDay)—Inclusion of endogenous hormones in prediction models improves prediction of invasive breast cancer risk in postmenopausal women, according to a study published online Aug. 18 in the Journal of ...

Novel oncogenic RET mutation found in small cell lung cancer

16 hours ago

For the first time an oncogenic somatic mutation at amino acid 918 in the RET (rearranged during transfection) protein has been identified in small cell lung cancer (SCLC) tumors and enforced expression of this mutation within ...

User comments