Current insights into epigenetics, noncoding RNA interactome and clinical pharmacokinetics of dietary polyphenols in cancer chemoprevention.

Several studies have reported the health-beneficial effects of dietary phytochemicals, namely polyphenols, to prevent various diseases, including cancer. Polyphenols, like (-)-epigallocatechin-3-gallate (EGCG) from green tea, curcumin from turmeric, and ellagic acid from pomegranate are known to act by modulating antioxidant, anti-inflammatory and apoptotic signal transduction pathways in the tumor milieu. The evolving literature underscores the role of epigenetic regulation of genes associated with cancer by these polyphenols, primarily via non-coding RNAs (ncRNAs), such as microRNAs (miRNA) and long noncoding RNA (lncRNA). However, there is little clarity on the exact role(s) played by these ncRNAs and their interactions with other ncRNAs, or with their protein targets, in response to modulation by these dietary polyphenols. Here, we review ncRNA interactions and functional networks of the complex ncRNA interactome with their targets in preclinical studies along with the role of epigenetics as well as key aspects of pharmacokinetics and phytochemistry of dietary polyphenols. We also summarize the current state of clinical trials with these dietary polyphenols. Taken together, this synthetic review provides insights into the molecular aspects underlying the anticancer chemopreventive effects of dietary polyphenols as well as summarizes data on novel biomarkers modulated by these polyphenols for preventive or therapeutic purposes in various types of cancer.

Current perspectives on interethnic variability in multiple myeloma: Single cell technology, population pharmacogenetics and molecular signal transduction.

Multiple myeloma (MM) is an aggressive cancer characterised by malignancy of the plasma cells and a rising global incidence. The gold standard for optimum response is aggressive chemotherapy followed by autologous stem cell transplantation (ASCT). However, majority of the patients are above 60 years and this presents the clinician with complications such as ineligibility for ASCT, frailty, drug-induced toxicity and differential/partial response to treatment. The latter is partly driven by heterogenous genotypes of the disease in different subpopulations. In this review, we discuss emerging single cell technologies and applications in MM, population pharmacogenetics of MM, resistance to chemotherapy, genetic determinants of drug-induced toxicity, molecular signal transduction, as well as the role(s) played by epigenetics and noncoding RNAs including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that influence the risk and severity of the disease. Taken together, our discussions further our understanding of genetic variability in 'myelomagenesis' and drug-induced toxicity, augment our understanding of the myeloma microenvironment at the molecular and cellular level and provide a basis for developing precision medicine strategies to combat this malignancy.

New vistas in malignant mesothelioma: MicroRNA architecture and NRF2/MAPK signal transduction.

Malignant mesothelioma (MM) is a cancer of the mesothelial lining of the pleura, peritoneum, pericardium and testes. The most common form is asbestos-linked MM that is etiologically linked to repeated asbestos exposure with a long latency period, although non-asbestos MM has also been reported. Late diagnosis, poor survival rates, lack of diagnostic and prognostic markers act as major impediments in the clinical management of MM. Despite advances in immune checkpoint inhibition and CAR T-cell-based therapies, MM which is of different histologic subtypes remains challenging to treat. We review microRNAs (miRNAs) and the miRNA interactome implicated in MM which can be useful as circulating miRNA biomarkers for early diagnosis of MM and as biomarkers for prognostication in MM. Further, we underscore the relevance of the NRF2/MAPK signal transduction pathway that has been implicated in MM which may be useful as druggable targets or as biomarkers of predictive response. In addition, since MM is driven partly by inflammation, we elucidate chemopreventive phytochemicals that are beneficial in MM, either via crosstalk with the NRF2/MAPK pathway or via concerted anticancer mechanisms, and may be of benefit as adjuvants in chemotherapy. Taken together, a multifactorial approach comprising identification of miRNA target hubs and NRF2/MAPK biomarkers along with appropriately designed clinical trials may enable early detection and faster intervention in MM translating into better patient outcomes for this aggressive cancer.