Restoring p53 activity in melanoma cells makes them more susceptible to chemotherapy and BRAF inhibitors
Identification of MDM4 as a very promising target for treatment of melanoma
- Date : 03 Aug 2012
- Topic : Melanoma
Treatment of melanomas is particularly difficult, because they are usually resistant against conventional chemotherapy treatments. Agnieszka Gembarska and Chris Marine of the University in Leuven, Belgium have found a new line of approach in which to treat these cancers, namely by combating the interaction between the protein MDM4 and the tumour suppressor p53.
Their research offers a new angle for the development of medication and confirms that combination therapies, including those using the recently developed BRAF inhibitors, hold the promise of further improvement of the clinical response to a treatment. This study was published in the authoritative journal Nature Medicine and will undoubtedly be followed with interest by the pharmaceutical industry.
According to the researchers, their results are important on two levels. From a scientific perspective, it is very important that they have been able at all to prove that p53 plays a role in the formation of melanomas. However, this research also offers perspectives for optimizing the existing treatment strategies for melanomas. The current treatment with BRAF inhibitors has positive effects on many of the patients, but most of them relapse after a few months. They may have discovered a way of preventing this relapse.
p53, MDM4 and the formation of cancer
Chris Marine and his team have a long standing interest in p53 - a master tumour suppressor protein. Mutations in the p53 gene are very common in many various types of cancer. Surprisingly, mutations in p53 are (almost) never seen in melanomas. Scientists suspected that melanomas had found an alternative way of bypassing the action of p53.
The protein MDM4 has a negative effect on the action of p53 and has been the scientific focus of the investigators from Leuven for many years. Agnieszka Gembarska and Chris Marine have now demonstrated that 65% of melanomas contain much higher concentrations of the MDM4 protein than normal cells. The scientists found a pharmacological way to inhibit the interaction between MDM4 and p53 and were thereby able to restore the tumour suppressive effect of p53 in melanoma cells.
Restoring p53 activity in the melanoma cells makes these cells more susceptible to chemotherapy and the BRAF inhibitors. In their research, the researchers were able to identify MDM4 as a very promising target for treatment of melanoma, as part of a combination therapy.
Thank you for rating!
You have already rated this page, you can only rate it once!