Melanoma research breakthrough gives hope for treatment

February 7, 2017 by Amanda Weaver
Melanoma research breakthrough gives hope for treatment
A melanoma tumour generated in the laboratory by a QUT-led research team. Credit: Queensland University of Technology

A QUT-driven project has identified the way in which melanoma cells spread, opening up new pathways to treatment via drugs to 'turn off' the invasive gene.

Led by Dr Aaron Smith from QUT's School of Biomedical Sciences within the Institute of Health and Biomedical Innovation at the Translational Research Centre, the project results have just been published in international journal EBiomedicine and could offer a new avenue for cancer treatment.

"Cancer is characterised by uncontrolled growth of but if uncontrolled growth was the only problem then would be easily treated with surgery in most cases," said Dr Smith who collaborated with colleagues from UQ, QIMR and Oxford University.

"What makes cancer deadly is its tendency to invade tissue and migrate to other regions of the body, a process we call metastasis. Metastatic melanoma is one of the most aggressive and difficult to treat of all .

"By examining melanoma tumour samples we know that some cells are primarily proliferative and some are more invasive and migratory. We also know some cells can switch between those two behaviours; in other words a cell capable of establishing a new tumour at the same site can change to be more invasive and facilitate the spread the cancer to other parts of the body.

"What we did not know though was the reason why this happened. Our research project has discovered the mechanism by which those switch behaviours.

"This is an important breakthrough as we have identified a 'druggable' target as part of this process. Preventing this switch to invasive behaviour will enable us to prevent metastatic spread of melanoma and potentially other cancer types as well."

Dr Smith explained the two types of behaviours were marked by the expression of two different regulatory factors MITF (proliferating cells) and BRN2 (invasive).

"BRN2 function reduces MITF expression to slow down proliferation and put the cells into invasive mode," he said.

"Our project has identified a pathway that allows BRN2 to do this, firstly by increasing the expression of another regulatory factor called NFIB that further controls an invasive program in these cells.

"An important target of NFIB is an enzyme called EZH2 which then produces global (wide ranging) changes to the cells activity. EZH2 favours the expression of invasive genes and also turns "off" MITF to prevent proliferation, further re-enforcing the invasive capability of the .

"Once cells migrate away from the tumour we believe they no longer receive the signal that triggered the switch so the system re-sets to the MITF driven proliferation state which will then allow a new tumour to form at the new site.

"We have evidence the NFIB-EZH2 pathway may also underpin metastasis of other cancer types as well such as lung cancer. The good news is there are drugs to chemically inhibit EZH2 which are already in pre-clinical trials and which could be used to block the invasion."

Explore further: Study reveals why cancer cells spread within the body

More information: Mitchell E. Fane et al. NFIB Mediates BRN2 Driven Melanoma Cell Migration and Invasion Through Regulation of EZH2 and MITF, EBioMedicine (2017). DOI: 10.1016/j.ebiom.2017.01.013

Related Stories

Study reveals why cancer cells spread within the body

January 17, 2017
Each day, more than 1,600 people die from cancer in the US, and 450 in the UK, mostly because the disease has spread beyond a stage when surgery is an effective cure and has become resistant to therapy. Despite decades of ...

Epigenetic changes promoting cancer metastasis identified

December 21, 2016
Latest University of Otago research is shedding new light on why and how cancer cells spread from primary tumours to other parts of the body. This phenomenon – known as metastasis – causes about 90 per cent of all cancer ...

Scientists find how cancer cells can shrug off physical constraints on growth and spread

January 5, 2017
Scientists have revealed how cancer cells are able to break free of the physical restraints imposed by their surroundings in order to grow and spread around the body.

Stem cell 'marking' study offers alterative hypothesis of cancer metastasis

January 18, 2017
Stem cells are among the most energetically activated, migratory and proliferative sub-populations of tumour cells, according to observations by scholars at the Biomedical Research Centre at the University of Salford.

A protein that defines the melanoma blueprint

November 18, 2016
The main goals of the Melanoma Group at the Spanish National Cancer Research Centre (CNIO) are to identify biomarkers of tumour progression and to validate novel therapeutic targets in melanoma. In particular, their research ...

Inhibition of EZH2 might be new therapy of multiple myeloma

January 12, 2017
In a study published in the scientific journal Oncotarget, researchers from Uppsala University show how the protein EZH2 affects the development of multiple myeloma, and that inhibition of EZH2 could be used as a new strategy ...

Recommended for you

New bowel cancer drug target discovered

October 17, 2017
Researchers at the Francis Crick Institute have discovered a new drug target for bowel cancer that is specific to tumour cells and therefore less toxic than conventional therapies.

Many pelvic tumors in women may have common origin—fallopian tubes

October 17, 2017
Most—and possibly all—ovarian cancers start, not in ovaries, but instead in the fallopian tubes attached to them.

Using artificial intelligence to improve early breast cancer detection

October 17, 2017
Every year 40,000 women die from breast cancer in the U.S. alone. When cancers are found early, they can often be cured. Mammograms are the best test available, but they're still imperfect and often result in false positive ...

Researchers find novel mechanism of resistance to anti-cancer drugs

October 17, 2017
The targeted anti-cancer therapies cetuximab and panitumumab are mainstays of treatment for advanced colorectal cancer, the second leading cause of cancer-related deaths in the United States. However, many patients have tumors ...

Biology of childhood brain tumor subtypes offers clues to precision treatments

October 17, 2017
Researchers investigating pediatric low-grade gliomas (PLGG), the most common type of brain tumor in children, have discovered key biological differences in how mutated genes combine with other genes to drive this childhood ...

New assay may boost targeted treatment of non-Hodgkin lymphoma

October 17, 2017
Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer and the most frequently diagnosed non-Hodgkin lymphoma worldwide (nearly 40% of cases). Recent advancements indicate that both the prognosis and choice of treatment ...

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.