Navigation Links
Study details genes that control whether tumors adapt or die when faced with p53 activating drugs

When turned on, the gene p53 turns off cancer. However, when existing drugs boost p53, only a few tumors die the rest resist the challenge. A study published in the journal Cell Reports shows how: tumors that live even in the face of p53 reactivation create more of the protein p21 than the protein PUMA; tumors that die have more PUMA than p21. And, for the first time, the current study shows a handful of genes that control this ratio.

"The gene p53 is one of the most commonly mutated cancer genes. Tumors turn it off and then they can avoid controls that should kill them. Fine: we have drugs that can reactivate p53. But the bad news is when we go into the clinic with these drugs, only maybe one in ten tumors actually dies. We wanted to know what genes fine-tune this p53 effectiveness," says Joaquin Espinosa, PhD, investigator at the University of Colorado Cancer Center, associate professor in the Department of Molecular, Cellular and Developmental Biology at CU Boulder, and the paper's senior author.

To answer that question, the group including first author Zdenek Andrisyk, PhD, postdoc in the Espinosa Lab, turned off every gene in the human genome in turn and asked if there were genes that, when deactivated, would tip the balance from p21 to PUMA, thus enhancing the likelihood of cell death.

"We found a couple dozen genes involved in this ratio genes that with p53 activated, lead to more p21 and better survival or more PUMA and more cell death," Espinosa says.

The hope is that in addition to drugs that reactivate the tumor-suppressor gene p53, patients could be given a second drug targeting genes that control this p21/PUMA ratio, thus making first drug more effective. Likewise, in cases in which toxicity in healthy tissue limits the use of p53 activating drugs, Espinosa's research could lead to new drugs that thumb the scale of the p21/PUMA ratio toward survival in these healthy tissues. Up or down: learning to adjust the ratio has immense promise.

The group's next step is likely repeating the genetic screen with additional tumor and healthy cell lines to discover which of their newly discovered candidate genes are common controllers of the p21/PUMA ratio across cancer types. And, interestingly, the same technique could be used to make many existing drugs more effective.

"With many of these molecularly targeted therapies, you want one effect but then you end up with many other possible effects," Espinosa says. (An example is the recently-reported side effect of low testosterone in male lung cancer patient taking the molecularly targeted drug crizotinib.) The genetic screening technique used in the Espinosa lab could help disentangle effect from side effect showing which secondary genes regulate the desired, tumor-killing response and which secondary genes lead to undesirable side-effects.

"Not only could this technique lead to drugs that decrease the side effects of targeted therapies, but if you're not limited by these side effects, you can simply give more drug, perhaps making existing drugs much more powerful," Espinosa says.


Contact: Garth Sundem
University of Colorado Denver

Related medicine news :

1. Study Suggests Vaccine May Help Kids With Brain Cancer
2. Study reveals how cancer drug causes diabetic-like state
3. Coffee Drinking in Pregnancy Wont Lead to Sleepless Baby: Study
4. Lower GI problems plague many with rheumatoid arthritis, Mayo Clinic study finds
5. Veggies Like Broccoli, Cabbage May Help Fight Breast Cancer: Study
6. No Added Cancer Risk From Hip Replacement Materials: Study
7. Reported Decline in U.S. Pneumonia Deaths May Be False: Study
8. Early Study Finds Some Promise for Lung Cancer Vaccine
9. Narcissists Often Ace Job Interviews, Study Finds
10. Sexual objectification of female artists in music videos exists regardless of race, MU study finds
11. Soy may alleviate hot flashes in menopause, large-scale study finds
Post Your Comments:
(Date:12/1/2015)... ... December 01, 2015 , ... Physicians’ Education Resource®, LLC ... today announced that the first annual School of Gastrointestinal Oncology™ (SOGO™) will be ... and treatment of gastrointestinal cancers are undergoing transformational change, providing oncologists with powerful ...
(Date:12/1/2015)... ... 2015 , ... Growth in medical payments per workers’ compensation claim in Louisiana ... and nonhospital care, according to a recent study by the Workers Compensation Research Institute ... found medical payments per claim with more than seven days of lost time continued ...
(Date:12/1/2015)... Illinois (PRWEB) , ... December 01, 2015 , ... ... and share medical images have been lifted as IMAGE Information Systems launches MED-TAB™ ... Society of North America Annual Meeting from November 29 to December 4, 2015. ...
(Date:12/1/2015)... (PRWEB) , ... December 01, 2015 , ... ... , Visage Imaging Inc. (“Visage”), a wholly owned subsidiary of Pro Medicus Ltd. ... results enhancements at the Radiological Society of North America (RSNA) 2015 annual meeting ...
(Date:12/1/2015)... , ... December 01, 2015 , ... ... solutions for the care management and population health arenas, is pleased to announce ... and cost containment services, has successfully implemented the ACUITY Complete Care™ Management to ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... Germany , December 1, 2015 /PRNewswire/ ... leading global manufacturer of eye and gaze tracking solutions, ... SMI remote eye trackers as a component of its ... concussions, eye sight, and medical and performance issues in ... part of SMI,s mass-market-ready eye tracking platform, which is ...
(Date:12/1/2015)... 1, 2015 --> ... van Leeuwenhoek Hospital (NKI-AVL), among the world,s largest ... Leksell Gamma Knife® Icon™, the company,s latest generation ... --> --> With the ... treatments, Leksell Gamma Knife Icon offers greatly enhanced ...
(Date:12/1/2015)... Dec. 01, 2015 ... "Drug Delivery Technology Market 2015 - Forecast ... --> ) has announced the addition ... - Forecast to 2020" report to their ... ) has announced the addition of the ...
Breaking Medicine Technology: