Researchers Identify CXCR4 as Weak Therapeutic Target for Pleural Mesothelioma

Researchers Identify CXCR4 as Weak Therapeutic Target for Pleural Mesothelioma

A new study reports that a protein formerly identified as a potential therapeutic target in pleural mesothelioma, CXCR4, might not be a relevant approach for the treatment of such patients.

Based on this study’s results, researchers say that CXCR4 does not seem to be a promising therapeutic option for patients with progressive, inoperable or chemotherapy-resistant pleural mesothelioma.

The study, “Targeting CXCR4 with [68Ga]Pentixafor: A suitable theranostic approach in pleural mesothelioma?,” was published in Oncotarget.

CXCR4 is highly produced in more than 20 tumor types, promoting tumor growth and progression, tumor invasiveness, and metastasis. That is what studies in lab-grown cells have shown. But a novel PET/CT imaging agent targeting CXCR4 in cancer mouse models and patients has shown otherwise.

Robust overexpression of CXCR4 has been reported in human mesothelioma cell lines and the majority of mesothelioma tissues, so researchers aimed to use this imaging agent, called [68Ga]Pentixafor to investigate the feasibility of CXCR4 as a therapeutic target in mesothelioma patients.

To assess CXCR4 as a potential therapeutic target, its levels were measured by PET/CT scans in six patients who never had received treatment. Five were males and one was female, with ages ranging from 54 to 80 years.

After imaging, surgery was performed in all patients and samples were collected to look for the quantity and distribution of the CXCR4 protein. In addition to the samples available from patients undergoing imaging, nine surgical mesothelioma samples from other patients (eight males and one female) were used.

Data from imaging and sample analysis seems to suggest a lower frequency of CXCR4 in mesothelioma cells than what had been reported previously. On the image analysis of the scans, none of the six patients presented relevant focal CXCR4-positive lesions. Regarding the tissue evaluation of membranous CXCR4, all samples were negative for CXCR4, but also no evidence of intracellular CXCR4 was found.

“In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy,” the researchers wrote.

CXCR4 is a protein that works as a receptor at the membranes of cells. CXCR4 and its ligand CXCL12 play an important role in several physiological processes that rely on the recruitment of various cells, such as stem cells, progenitor cells and immune cells.

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