Navigation Links
Targeted therapy reactivates 'guardian of the genome' in resistant cancer
Date:11/15/2010

It is common for cancer cells to find some way to disarm p53, also known as "guardian of the genome" due to its action in preventing defective cells from dividing. "The critical importance of the protective function of p53 is underscored by the diversity of molecular strategies employed by cancer cells to subvert p53 activity, such as overexpression of antagonistic proteins like HDM2 and HDMX," explains senior study author Dr. Loren D. Walensky from Harvard Medical School. "Restoration of p53 activity remains an important goal in the quest for more effective cancer therapeutics."

Previous work demonstrated that selective inhibition of HDM2 restored p53 function in cancer cells. However, these results were often compromised by expression of HDMX. In an earlier study, Dr. Walensky and colleagues described the generation of "stapled" peptides designed to resemble the section of p53 that interacts with HDM2. When biochemical and structural studies revealed that HDM2 and HDMX engage the same region of p53, the researchers examined whether the most effective engineered HDM2 inhibitor (SAH-p53-8) could also interfere with HDMX and how this interaction might influence the p53 activity.

The SAH-p53-8 compound was even more effective at targeting HDMX and effectively blocked formation of the inhibitory p53-HDMX complex, thereby restoring the p53 pathway and reducing tumor cell viability. Importantly, when SAH-p53-8 was delivered intravenously to mice with HDMX-expressing cancer, p53 activity was increased and tumor growth was suppressed.

"We found that targeting HDMX overcame HDMX-mediated p53 suppression and resistance to selective HDM2 inhibition, while dual targeting of HDM2 and HDMX maximized therapeutic reactivation of the p53 tumor suppressor pathway in cancers that express both protein antagonists and retain functional p53," concludes Dr. Walensky. "Importantly, monitoring cellular levels of p53-HDMX complex may be useful for predicting cancer cell susceptibility to HDMX inhibition and determining the efficacy of HDM2 inhibitor-mediated p53 restoration, which forms the basis for enhancing the therapeutic impact of dual HDM2/HDMX targeting in resistant cancers."


'/>"/>

Contact: Elisabeth N. Lyons
elyons@cell.com
617-386-2121
Cell Press
Source:Eurekalert

Related medicine news :

1. UCI non-small cell lung cancer study highlights advances in targeted drug therapy
2. People with specific kind of lung cancer respond to new targeted treatment
3. Targeted radiation therapy minimizes GI side effects for prostate cancer patients, Penn study shows
4. Highly targeted radiation technique minimizes side effects of prostate cancer treatment
5. Sexual issues a major concern for cancer patients taking new targeted drugs
6. Targeted therapy promising for HER2-positive metastatic breast cancer
7. Evaluation of targeted therapy in ovarian cancer
8. Moffitt Cancer Center and GLG Pharma LLC sign licensing agreement to develop the next generation of targeted anti-cancer therapeutics
9. Moffitt Cancer Center and GLG Pharma, LLC sign licensing agreement to develop the next generation of targeted anti-cancer therapeutics
10. Targeted therapy triggers complex mechanism of resistance
11. Synthetic lethality strategy improves molecularly targeted cancer therapy
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2016)... (PRWEB) , ... May 24, 2016 , ... ... expansion of its services to provide one resource, from start to finish, for ... preparation, Life Safety Statement of Condition surveys requested by the Joint Commission, and ...
(Date:5/24/2016)... ... 24, 2016 , ... i2i, a national leader in population ... “Transforming Outcomes” User Conference in Las Vegas on May 19-20, 2016. The ... the market standard for meaningful population health management. The company recently closed ...
(Date:5/24/2016)... ... May 24, 2016 , ... ... is pleased to welcome new Partner Firm Austin & Co., Inc. Headquartered ... to insurance, employee benefits, HR consulting, benefits technology, and beyond. As an ...
(Date:5/24/2016)... ... May 24, 2016 , ... Educational opportunities, and therefore ... more advantaged communities providing richer opportunities. Recognizing the key role of housing in ... policies; (b) school choice policies; (c) school desegregation policies; (d) wealth-focused policies; and ...
(Date:5/24/2016)... (PRWEB) , ... May 24, 2016 , ... How to ... · Raleigh, NC, http://www.fdanews.com/humanerrordrugdevice , Human error is known to be the ... that human error will ever be totally eliminated, many human performance problems can be ...
Breaking Medicine News(10 mins):
(Date:5/23/2016)... SAN FRANCISCO , May 23, 2016 ... expected to reach USD 5.0 billion by 2022, according ... The increasing generation of medical waste coupled with the ... healthcare industry is expected to drive the demand for ... with these devices as compared to that of the ...
(Date:5/20/2016)... 2016 The Biotech arena remains ... the industry is not far from recovering. There are ... the following four equities: Anacor Pharmaceuticals Inc. (NASDAQ: ... ), Aralez Pharmaceuticals Inc. (NASDAQ: ARLZ ), ... Sign up for your free trading alerts on these ...
(Date:5/19/2016)... , May 19, 2016  According to the ... the world lacks basic diagnostic imaging. Whereas mammography ... the United States , many places ... technology. In fact, the WHO reports that those ... avoidable or treatable death, simply due to the ...
Breaking Medicine Technology: