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:1/23/2017)... NY (PRWEB) , ... January 23, 2017 , ... ... today that John J. Nelson, a senior accountant at the Firm, will participate in ... Make-A-Wish® Hudson Valley. Over 200 runners will race up 1,576 steps, a vertical distance ...
(Date:1/23/2017)... ... 23, 2017 , ... Wooden and plastic balance boards have been around since at least the ... Board is the first and only balance board to use a patent-pending design featuring ... at the same time as well as skill-level adjustable for all ages and abilities. ...
(Date:1/23/2017)... ... January 23, 2017 , ... ... Crystallization in Process Chemistry by Applying Simple PAT Tools . , ... to isolate and purify the desired product. Chemists now spend more time ...
(Date:1/23/2017)... , ... January 23, 2017 ... ... Foundation (OREF), in partnership with the American Society of Anesthesiologists® (ASA®), the ... (APSF), the American Academy of Orthopaedic Surgeons (AAOS) and the Cigna Foundation, ...
(Date:1/23/2017)... ... ... “Life Under Blankets”: an entrancing story about one woman's travels through the wilderness ... of published author, Kimberly Mitchell, who earned her bachelor’s degree in English education at ... master’s degree in education in the field of curriculum and instruction. Kimberly’s passion for ...
Breaking Medicine News(10 mins):
(Date:1/21/2017)... , Jan. 20, 2017 ResMed (NYSE: RMD ... ( Winter Haven, Florida ) today announced they have ... BMC and 3B will be permitted to sell their existing products ... a one-time settlement payment to 3B to close the ... not include an admission of liability or wrongdoing by any party. ...
(Date:1/21/2017)... Research and Markets has announced the addition ... Technology, Route Of Administration, End User - Forecast to 2025" ... ... at a CAGR of around 7.8% over the next decade to ... report analyzes the global markets for Advanced Drug Delivery across all ...
(Date:1/20/2017)... , Jan. 20, 2017  Ethicon Endo-Surgery, ... Megadyne Medical Products, Inc., a privately held ... markets electrosurgical tools used in operating rooms ... of Ethicon,s* advanced energy devices with Megadyne,s ... major step forward in Ethicon,s goal to ...
Breaking Medicine Technology: