New line of approach for combination therapy against melanoma

July 23, 2012, VIB (the Flanders Institute for Biotechnology)

​A melanoma is a malignant form of skin cancer and is one of the most aggressive types of tumors there is. Treatment is particularly difficult, because melanomas are usually resistant against conventional chemotherapy treatments. Agnieszka Gembarska and Chris Marine

(VIB/KU Leuven) have found a new line of approach in which to treat these aggressive skin cancers, namely by combating the interaction between the MDM4 and the tumor 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 . This study was published in the authoritative journal Nature Medicine and will undoubtedly be followed with interest by the pharmaceutical industry.

Chris Marine: "Our results are important on two levels. From a scientific perspective, it is very important that we have been able to prove that p53 plays a key role in the formation of . However, this research also offers perspectives for optimizing the existing treatment strategies for melanomas. The current treatment with BRAF inhibitors has positive effects on nearly 80% of the patients, but many of them relapse after a few months. We may have discovered a way of preventing this relapse".

p53, MDM4 and the formation of cancer

Chris Marine and his team has a long standing interest in p53 - a master tumor suppressor protein (in other words a protein that counteract the formation of cancer). 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 VIB investigators 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 tumor suppressive effect of p53 in melanoma cells.

Chris Marine: "The restoration of the p53 activity in the melanoma cells makes these cells more susceptible to chemotherapy and the BRAF inhibitors. In our research, we were able to identify MDM4 as a very promising target for treatment of melanoma, as part of a combination therapy.

Explore further: New drug shrinks cancer in animals, study shows

Related Stories

New drug shrinks cancer in animals, study shows

April 6, 2011
A study led by researchers at the University of Michigan Comprehensive Cancer Center showed in animal studies that new cancer drug compounds they developed shrank tumors, with few side effects.

Recommended for you

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.