Navigation Links
National Cancer Centre Singapore scientists discover p53 mutation hinders cancer treatment response
Date:1/25/2013

Reducing the level of mutant p53 gene increases susceptibility to treatment

Scientists from the National Cancer Centre Singapore (NCCS) have discovered the workings of the gene that has been hindering treatment response in cancer patients. This discovery was made after 5 years of studying the mutant form of the p53 gene, the major tumor suppressor in humans, which is generally found mutated in over 50% of all type of human cancers.

The dominant-negative (DN) effect of the mutant p53 gene in cancers was found to affect the outcome of cancer treatment modalities. DN effect is a phenomenon whereby one copy of mutant p53 that exists in cancer cells inhibits the tumor suppressor activity of the other wild-type p53 copy when they co-exist. The result is that a patient may either have poor response or earlier relapse of tumours after their treatment.

The research findings is significant in that it offers hope to improve cancer treatment outcomes by selectively inhibiting mutant p53's DN effect through several methods by generating selective and specific inhibitory molecules specific for some of the common hot-spot p53 point mutations. There are currently no drugs or compounds that can alleviate DN effects of mutant p53.

In order to understand the specific roles of mutant p53 DN properties in regulating acute treatment response and long-term tumourgenesis, a team of five researchers led by NCCS Prof Kanaga Sabapathy, the Principal Investigator in the Laboratory of Carcinogenesis and Head of the Division of Cellular & Molecular Research from NCCS, carried out experiments by generating genetically engineered knock-in mouse strains expressing varying levels of mutant p53. The results showed that DN effect is observed after acute p53 activation by a variety of chemotherapeutic drugs and irradiation, thereby affecting anti-cancer treatment. This breakthrough came after five years of intensive research.

It was found that mutant p53 have DN effects in a cell-type and dose-dependent manner, especially during acute p53 activation where p53 levels are elevated. Based on the above observations, efforts to generate specific inhibitors for the common hot spot p53 point mutations are underway. The inhibition of mutant p53 expression in cells carrying a wild-type and mutant p53 alleles can improve response to chemotherapeutic drugs.

In a further study, the researchers also questioned the possibility of the mutant p53 acquiring new functions (or Gain of Function) to drive carcinogenesis, transforming normal cells to cancerous cells. Their investigation comparing cells from genetically engineered mouse strains expressing 2 different types of p53 mutations: the R172H mutation versus the R246S mutation, which showed that Gain of Function (GOF) was found only in the former. This showed that GOF of mutated p53 is specifically dependent on mutation-type but not across all kinds of genetic mutations, highlighting diversity in properties of the different types of p53 mutations, thereby indicating that mutations found in human cancers can behave differently, and thus, need to be carefully assessed prior to treatment.

Thus, the existence of mutant p53 certainly has a negative impact on cancer treatment, whether it is through DN effect or GOF. Prof Sabapathy said that the team is now embarking on more research to determine the possibility of targeting mutant p53 without affecting wild-type p53 in human cells, paving way to clinical trials in the future to test the efficacy on cancer therapeutic response.


'/>"/>
Contact: Rachel Tan
Rachel.Tan.C.H@nccs.com.sg
65-623-69535
SingHealth
Source:Eurekalert

Related medicine news :

1. MU receives national award for using mind-body approach to improve health
2. International breast health global summit will focus on supportive care and quality of life
3. International conference to explore health of descendants of transatlantic slave trade
4. National poll: Low cost, lifesaving services missing from most older patients health care
5. UT MD Anderson President Ronald DePinho elected to National Academy of Sciences
6. Kessler Foundation researchers present at first International Congress on Cognition in MS
7. Dr. Yael Mosse will receive first Nachman Award in Pediatric Oncology at national conference
8. Georgetown physician leads national resveratrol study for Alzheimers disease
9. National initiative launched to change the way biology departments approach undergraduate education
10. Boston researcher, surgical oncologist receives national award
11. Internationally known expert in ovarian cancer to be honored at the ASCO Annual Meeting
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... Aliso Viejo, California (PRWEB) , ... June 25, 2016 , ... ... preset to fit their specific project," said Christina Austin - CEO of Pixel Film ... all fully customizable and all within Final Cut Pro X . Simply select ...
(Date:6/25/2016)... ... June 25, 2016 , ... Conventional wisdom preaches the ... In terms of the latter, setting the bar too high can result in disappointment, ... just slow progress toward their goal. , Research from PsychTests.com reveals ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... Sessions in Dallas that it will receive two significant new grants to support ... as PHA marked its 25th anniversary by recognizing patients, medical professionals and scientists ...
(Date:6/24/2016)... Plano, TX (PRWEB) , ... June 24, 2016 , ... ... taking part in Genome magazine’s Code Talker Award, an essay contest in which patients ... for an award to be presented at the 2016 National Society of Genetic Counselors ...
(Date:6/24/2016)... ... 2016 , ... National recruitment firm Slone Partners is pleased to ... genomics experience, as Vice President of North American Capital Sales at HTG Molecular ... the sales team in the commercialization of the HTG EdgeSeq system and associated reagents ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 ... the "Structural Electronics 2015-2025: Applications, Technologies, Forecasts" ... In-Mold Electronics, Smart Skin, Structural ... Structural electronics involves electronic and/or ... protective structures, replacing dumb structures such as vehicle ...
(Date:6/24/2016)... June 24, 2016 According to ... Type (Standard Pen Needles, Safety Pen Needles), Needle Length ... Growth Hormone), Mode of Purchase (Retail, Non-Retail) - Trends ... report studies the market for the forecast period of ... USD 2.81 Billion by 2021 from USD 1.65 Billion ...
(Date:6/23/2016)... -- Research and Markets has announced the addition ... 2022" report to their offering. ... with kidney failure, it replaces the function of kidneys by ... and thus the treatment helps to keep the patient body,s ... Increasing number of ESRD patients & substantial healthcare ...
Breaking Medicine Technology: