Melanoma is the most lethal skin cancer, and is diagnosed at rates higher than any other cancer type. If it is caught before the cancer has spread through a process called metastasis, 99.5% of people diagnosed with it survive for five years or more. Once melanoma metastasizes, however, survival rates plummet to 32%.
Dario Marchetti, PhD, and his team at The University of New Mexico Comprehensive Cancer Center study how tumors metastasize, and they wanted to find a way to predict which melanomas are likely to metastasize.
In a paper published in Cancer Research Communications, Marchetti and his colleagues describe the process they used to identify the genetic signs of melanoma that is likely to spread. This process can be used for other types of cancer and metastases.
Marchetti’s research focuses on circulating tumor cells. These cells are shed from a cancer tumor, travel through the bloodstream and lodge themselves in distant regions of the body where they can start a new tumor.
Most circulating tumor cells die in the bloodstream, however – very few survive to colonize new tissues in the body, says Marchetti. So finding circulating tumor cells in a sample of blood is painstaking at best.
Marchetti and his team created a process to isolate circulating tumor cells from people with melanoma. They chose people who represented a range of stages, from primary to metastatic melanoma.
They then injected these circulating tumor cells into mice and watched for melanoma tumors in the brain using MRI scans. Interestingly, these mice had brain tumor patterns that matched the human patterns of melanoma that spreads to the brain.
“These patterns of brain metastasis – cerebellum, frontal lobe, temporal lobe – recapitulated results for clinical melanoma,” Marchetti says. And that means that predicting metastasis in mice can be translated into predicting metastasis in people, he says.
So Marchetti and his team took circulating tumor cells from these mice and compared them to circulating tumor cells taken from the people with melanoma. They looked at the cells’ genomic signatures – their DNA and the messenger RNA that cells use to make proteins.
They found the same common genomic signature in the circulating tumor cells taken from the mice and from the people with melanoma brain metastases. And they found this signature in the circulating tumor cells that were injected in the mice, as well as in cells isolated from a person with melanoma brain metastasis who was undergoing treatment.
That genomic signature included several genes that are involved in regulating ribosomes, the cellular structures called organelles that assemble proteins.
The genomic signature did not match that of circulating tumor cells taken from the people whose melanoma had not metastasized. This means that the circulating melanoma tumor cells that led to brain metastasis in mice and in humans are different from those circulating tumor cells that don’t cause metastasis.
“This finding is relevant”, Marchetti says, “because we find it in several conditions, regardless of person or of mouse. It’s potentially huge and needs to be confirmed in larger numbers of people.”
Although these results are exciting, Marchetti stresses that much more work needs to be done to confirm them and to develop blood tests or treatments for metastasizing melanoma.
As a bonus, he says the process that he and his team developed is not limited to melanoma or to brain metastases. It could be used for other types of cancer and for metastases to other organs.
Not wasting any time, Marchetti and his team have already started on that further work.
About Dario Marchetti, PhD
Dario Marchetti, PhD, holds a doctorate from the University of Pavia, Italy, and completed postdoctoral fellowships at University of Illinois-Chicago, MD Anderson Cancer Center and Baylor College of Medicine in Houston, holding faculty appointments there. In 2019, he joined UNM, where he is a tenured Professor in the Departments of Internal Medicine and Pathology. Dr. Marchetti is a recognized expert and international authority in the biology and clinical utilities of Circulating Tumor Cells (CTCs) directly isolated from blood of cancer patients.
Paper Reference
"The RPL/RPS gene signature of melanoma CTCs associates with brain metastasis" was published online on November 2, 2022, in Cancer Research Communications. (https://aacrjournals.org/cancerrescommun). Authors are: Tetiana Y. Bowley, Irina V. Lagutina, Carol Francis, Sinduja Sivakumar, Reed G Selwyn, Erik Taylor, Yan Guo, Bridget N. Fahy, Bernard Tawfik, and Dario Marchetti.
UNM Comprehensive Cancer Center
The University of New Mexico Comprehensive Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in a 500-mile radius.
Its more than 136 board-certified oncology specialty physicians include cancer surgeons in every specialty (abdominal, thoracic, bone and soft tissue, neurosurgery, genitourinary, gynecology, and head and neck cancers), adult and pediatric hematologists/medical oncologists, gynecologic oncologists, and radiation oncologists. They, along with more than 600 other cancer healthcare professionals (nurses, pharmacists, nutritionists, navigators, psychologists and social workers), provide treatment to 65% of New Mexico’s cancer patients from all across the state and partner with community health systems statewide to provide cancer care closer to home. They treated almost 15,000 patients in more than 100,000 ambulatory clinic visits in addition to in-patient hospitalizations at UNM Hospital.
A total of nearly 1,855 patients participated in cancer clinical trials testing new cancer treatments that include tests of novel cancer prevention strategies and cancer genome sequencing.
The more than 123 cancer research scientists affiliated with the UNMCCC were awarded $38.2 million in federal and private grants and contracts for cancer research projects. Since 2015, they have published nearly 1000 manuscripts, and promoting economic development, they filed 136 new patents and launched 10 new biotechnology start-up companies.
Finally, the physicians, scientists and staff have provided education and training experiences to more than 500 high school, undergraduate, graduate, and postdoctoral fellowship students in cancer research and cancer health care delivery.