In the last year, researchers have been looking closely at the cellular process of metastasis. This spread of cancer within the body to distant sites makes therapeutic approaches more complicated. Metastases remain difficult to treat for all cancer types, hence to examination into the process of metastasis to attempt to inhibit it before the process starts. One area of focus is the perinucleolar region, which is usually referred to as the perinucleolar compartment (PNC). This structure is located within the nucleus of a cancer cell. Most of us learn about the nucleus and perhaps many also know the nucleolus. The nucleus is where our DNA is stored. The nucleolus is a small, usually spherical, structure within the nucleus; it is the site of rRNA transcription, processing, and ribosomal generation in transformed or various cancer tissues. It is visualized microscopically when a cell is in interphase and is rarely found in normal cells.
The critical component within the PNC identified recently is a compound called metarrestin. According to the authors of the study, metarrestin disrupts the nucleolar structure and inhibits RNA polymerase I transcription via a translation elongation factor called eEF1A2. Researchers found that metarrestin inhibited cancer cell invasion in vitro and in three separate mouse models of human cancer. One of the mouse models had metastatic pancreatic cancer and survival was extended; the study also found that no organ toxicity or adverse effects were observed.
The newest study, published May 16, 2018, in the journal Science & Translational Medicine looked at pancreatic cancer effects in mouse models as described. Additional research has been published in the past year with focus on other mouse models of cancer including lung and liver metastases of prostate cancer and breast cancer. Liver histology reports included in the newest study show the metastatic tumors in liver tissue prior to treatment with metarrestin. The after-treatment histology shows significant reduction in tumor presence. Therefore, a novel approach to metastasis treatment could be to disrupt the protein-making apparatus within the metastatic cell itself. If it cannot produce proteins and replicate itself, the cell fails to thrive and so growth stalls.
The group working on this research are collaborators from the National Institutes of Health, Northwestern University Feinberg School of Medicine, the National Center for Advancing Translational Sciences (NCATS)- Chemical Genomic Center, and the NCATS-Bridging Interventional Development Gaps program. Together these professionals are gathering data on metarrestin needed to further its development as a clinical drug including application to the Federal Drug Administration for an Investigational New Drug status. These are the steps needed to start the process of using metarrestin on patients as part of clinical trials.
Sources: Science & Translational Medicine, NIH National Center for Advancing Translational Sciences, Gynecologic Oncology, Cancer Research, Cold Spring Harbor Perspectives in Biology Journal,