Melanoma is a leading cause of skin cancer deaths worldwide – largely because physicians and researchers have yet to determine how to control the rapid spread of cancer from the original site to tumors throughout the body. Patients diagnosed with advanced stage metastatic melanoma have a median survival time of six months or less.

A key factor responsible for this low survival time is that while many melanoma tumors respond to an initial treatment by front-line anti-melanoma drugs, there is frequently a recurrence of the tumor that no longer responds to the treatment. This leads to a drug resistant, more invasive form of melanoma. Anticancer drugs kill many of the melanoma cancer cells when first used, but sometimes leave behind a small population of cancer cells that are drug resistant. These cells are similar to stem cells, critical during embryonic development. These surviving, stem cell-like cancer cells can give rise to a recurrence of the melanoma that is drug resistant and metastatic.

New research, published this week in Laboratory Investigation (Nature Publishing Group) may hold the key to this challenge. The investigation was an international effort led by Mary J.C. Hendrix, president of Shepherd University; her laboratory partners at West Virginia University, Richard Seftor, Elisabeth Seftor and Naira Margaryan; and a team of collaborators in Chicago, Boston and Australia.

The research team studies a protein long known to be active in embryonic development, called Nodal, that also has a critical role in aggressive human cancer. Their latest paper shows that the current front-line cancer therapies employed by physicians do not reduce Nodal levels in aggressive tumor cells. It suggests that a combination of treatments that both target Nodal-positive melanoma cells and other surrounding cancer cells will be the most effective therapy to successfully halt the progression of melanoma from a single cancer site to distant sites, resulting in the suppression of metastasis.

“Targeting melanoma with front-line therapy does not abrogate Nodal-expressing tumor cells” was authored by Mary J.C. Hendrix, Irawati Kandela, Andrew P. Mazar, Elisabeth A.Seftor, Richard E.B. Seftor, Naira V. Margaryan, Luigi Strizzi, George F. Murphy, Georgina V. Long, and Richard A. Scolyer.Laboratory Investigation advanced online publication October 24, 2016; doi:10.1038/labinvest.2016.107.

About the authors: Mary Hendrix, Richard Seftor, Elisabeth Seftor and Naira Margaryan (formerly at Ann and Robert H. Lurie Children’s Hospital and Northwestern University Feinberg School of Medicine) have their research laboratory at West Virginia University, Robert C. Byrd Health Science Center; Luigi Strizzi is located at Midwestern University; George Murphy’s laboratory is located at Harvard Medical School, Brigham & Women’s Hospital; Andrew Mazar (formerly at Northwestern University) is now at Monopar Therapeutics, Inc.;  Irawati Kandela is at Northwestern University; and Georgina Long and Richard Scolyer are associated with the Melanoma Institute Australia and Sydney Medical School, The University of Sydney.

This work was supported by the H Foundation and Dixon Translational Grants Initiative (to MJCH), and NCI CCSG P30 CA060553 (to APM)