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Insights Into Therapeutic Resistance in Leptomeningeal Melanoma Metastases

By: Cordi Craig
Posted: Friday, February 7, 2020

A new study, published in Clinical Cancer Research, identified transcriptional signatures in the cerebrospinal fluid of patients with leptomeningeal melanoma metastases, a rare late-stage complication for which little clinical information exists. Patients who are diagnosed with this disease have a poor prognosis and no current effective therapies. The results suggest there may be molecules within the cerebrospinal fluid of patients that stimulate cancer cell survival and prevent responses.

“It is likely that the environment of leptomeningeal melanoma metastases is a key regulator of both disease progression and therapeutic response,” explained Keiran S.M. Smalley, PhD, of The Moffitt Cancer Center & Research Institute, Tampa, Florida, in a Moffitt press release. “Improved knowledge about the microenvironment of leptomeningeal melanoma metastases may allow novel therapeutic strategies to be developed that can delay disease progression.”

The research team collected 45 cerebrospinal fluid samples from 16 patients. Half of the enrolled patients had confirmed leptomeningeal melanoma metastases, and the researchers compared the molecular profiles of the samples between the two groups. The majority of patients with confirmed disease (n = 7) had poor survival rates and died within 4 months. However, a single patient responded well and was alive more than 35 months after diagnosis.

Using mass spectrometry, the researchers found that the cerebrospinal fluid of patients with the disease was enriched for pathways involved in innate immunity, protease-mediated damage, and IGF-related signaling. When the cerebrospinal fluid of nonresponding patients with the disease was incubated with melanoma cells, the fluid induced the activation of proteins and signaling pathways for melanoma progression. One of the survival molecules may be TGF-β. The patient who responded had undetectable levels of TGF-β, whereas those patients who did not respond to treatment had much higher levels of TGF-β.

Disclosure: For full disclosures of the study authors, visit clincancerres.org.



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