Prostate cancer has a global prevalence and is a leading cause of cancer death in men. Various therapeutic approaches for the treatment of prostate cancer have gained acceptance. For example, High-intensity focused ultrasound (HIFU) has recently risen as a therapy option. HIFU is a new treatment for prostate cancer that utilizes ultrasonic therapy to target cancerous cells. Another widely used treatment is deprivation of androgen hormone for advanced stages of prostate malignancies. The use of hormone deprivation therapy slows down malignant growth, but it also increases the incidence of castration-resistant prostate cancer (CRPC).
Prostate Cancer
PARPi (poly (ADP-ribose) polymerase inhibitors) are currently a very promising targeted therapy for metastatic castrate-resistant prostate cancer (mCRPC). Because PARPi is limited to a subset of individuals with abnormalities in their homologous recombination system, it has some therapeutic limitations.
Recent research studies have targeted MALAT1, which multiplies in advanced stages of prostate cancer growth, and its effects on PARPi.
Inhibiting homologous recombination by targeting MALAT1 adds sensitivity to PARP inhibitors
Researchers in this study discovered some genes linked to progressive stages in prostate cancer. These genes are the MALAT1 genes. The MALAT1 genes led to a poor prognosis in cancer recovery in the study. The levels of MALAT1 were significantly more in the progressed stages of metastatic prostate cancers in the system than in localized cases of malignancies. There are also regulation changes of gene expression in metastatic prostate cancer cases. The genes are regulated upwards more in metastatic prostate cell malignancies. Clinical indicators of pathologies are associated with gene expression. The event of prostate cancer re-occurring is influenced by the MALAT1 levels biochemically. The recurrence was significant in patients with high MALAT1 genes.
The MALAT1 genes are metastasis-promoting IncRNA in varieties of cancers. The genes predict treatment responses. There are co-morbidities of lymphoma metastasis, recurrence of the disease, and therapy failure in tumors with increased MALAT1 gene levels. The deficiency of the gene disrupts the cell’s ability to heal. Prostate cells with depleted MALAT1 had an increase in dead cells. Also discovered was the elevation of the number of PARP, indicating cell death. The study reports that MALAT1 genes contribute to genomic integrity.
MALAT1 expression is significantly high in individuals with metastatic prostate cancer. These high expressive rates contribute to the disease’s aggressiveness and therapeutic failure. With lower levels of MALAT1, the sensitivity of chemotherapeutic medicines improves.
Clinical significance
MALAT1 gene is a recovery factor for cancer. Its expression results in a poor prognostic outcome for prostate cancer. MALAT1 gene is also necessary for the growth of metastatic cancers; they cannot survive without it. The malignant cells solely require the expressions of genes. MALAT1 gene appears present in the carcinogenesis of various cancers, including prostate, lung, pancreatic, and cervical malignancies.
Conclusion
Research has shown that downregulation of MALAT1 significantly improves prognostic outcomes for patients. It also decreases stemness while conferring chemotherapeutic sensitivity. In prostate malignancies, lowering homologous recombination by targeting MALAT1 increases sensitivity to PARP inhibition. The targeting of MALAT1 genes leads to better recovery chances for people with prostate cancer.
References
Targeting MALAT1 Augments Sensitivity to PARP Inhibition by Impairing Homologous Recombination in Prostate Cancer
Anjali Yadav, Tanay Biswas, Ayush Praveen, Promit Ganguly, Ayushi Verma, Dipak Dutta, Bushra Ateeq
bioRxiv 2022.06.01.494272; doi: https://doi.org/10.1101/2022.06.01.494272
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