A recent study published in Molecular Cancer Research, led by researchers from the laboratory of Mary J.C. Hendrix, found that standard treatments to address metastatic melanoma are ineffective against Nodal, a growth factor protein. Further, this study also revealed that combination therapies that include anti-Nodal antibodies and DTIC offer a very promising alternative. Previous research projects from the Hendrix laboratory proved that Nodal is essential for human embryonic development and that it re-emerges in metastatic melanoma.

Metastatic melanoma is the number one cause of skin cancer deaths in the United States. As soon as melanoma is metastasized and spreads, a patient’s life expectancy becomes dramatically shortened. Currently, the standard therapy for patients that receive a metastatic melanoma diagnosis is Dacarbazine (DTIC), however, the drug is associated with poor patient outcomes.

Katharine Hardy, a post-doctoral fellow in the Hendrix laboratory, administered treatment to 3 different melanoma cell lines with DTIC. The researchers found that Nodal-expressing cells remained after the therapy and its numbers increased. “Remarkably, the residual populations of tumor cells that were largely unaffected by DTIC were Nodal positive,” said Hendrix in a press release.

The researchers’ next step was to evaluate and test if a combination of anti-Nodal and DTIC therapy could more successfully fight Nodal. “We found that using a lower concentration of the DTIC with a low concentration of an anti-Nodal antibody induced cell death and decreased cell growth synergistically. Tumor cells are very dependent on this growth factor, and when you take it away, they die,” noted Hendrix.

At any assessed time, melanoma tumor cells express about 20 to 30 percent of Nodal, according to the study. Nodal’s power is significant since it can increase cell proliferation and can spread to neighbor cells that don’t produce the growth factor themselves.

The researchers also started to investigate if other melanoma therapies available on the market could affect Nodal, and, if they couldn’t, they started to determine if therapies work together with anti-Nodal antibodies in a way similar to the DTIC study. They found that a combination strategy worked against Nodal and if experts can develop an anti-Nodal antibody suited for humans, it could imply better outcomes for those suffering with metastatic melanoma.

“Nodal is still a relatively new observation — made right here at Northwestern University and Stanley Manne Children’s Research Institute, and it’s a very powerful growth factor that represents a promising cancer stem cell target,” concluded Hendrix.

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