Current Topics in Medicinal Chemistry - Volume 18, Issue 30, 2018

Since their discovery in the 1990's, the study of a class of non-coding, single-stranded RNAs, christened the microRNAs has opened up new vistas in the field of cancer biology. MicroRNAs bind to their target mRNAs to act as either oncogenes or tumour suppressors. With the near-complete elucidation of the biogenesis pathway, and the advent of rapid sequencing technologies, microRNAs have slowly cemented their place as essential biomarkers for delineating the progression, metastasis, relapse or drug resistance of cancer. Being crucial players in the cancer pathway, there has been considerable urgency in designing molecules - both at the nucleotide and non-nucleotide level to counter the effects of their binding. A number of different approaches have yielded quite a body of compounds which have been found to be effective in the treatment of various tumours across many different organs. In this study, the focus is on the review of the timeline of discovery and characterization of microRNAs, underlining their importance in different cancers, shedding light on the discovery of anti-microRNA compounds and illustrating their uses in deriving new strategies to combat cancer.

The resistance to chemotherapeutics by the cancerous cells has made its treatment more complicated. Animal venoms have emerged as an alternative strategy for anti-cancer therapeutics. Animal venoms are cocktails of complex bioactive chemicals mainly disulfide-rich proteins and peptides with diverse pharmacological actions. The components of venoms are specific, stable, and potent and have the ability to modify their molecular targets thus making them good therapeutics candidates. The isolation of cancer-specific components from animal venoms is one of the exciting strategies in anti-cancer research. This review highlights the identified venom peptides and proteins from different venomous animals like snakes, scorpions, spiders, bees, wasps, snails, toads, frogs and sea anemones and their anticancer activities including inhibition of proliferation of cancer cells, their invasion, cell cycle arrest, induction of apoptosis and the identification of involved signaling pathways.

Nature has been a source of a wide range of products being utilized for the treatment of various diseases like malaria, cancer, diabetes etc. Among these, cancer is emerging as a leading cause of deaths worldwide and the development of cross-resistance to already established drugs increases the need for novel anticancer drugs. To discover novel anticancer molecules, it is a necessity to unearth the molecules which can act as anticancer agents. Taking natural products in vision, phytoconstituents like terpenoids, flavones, glycosides and alkaloids might act as a major source of lead molecules. Considering the anticancer prospectives of phytoconstituents, different unknown lead molecules are summarized in this review. The present review highlights the representative studies of plant-based anticancer agents which are classified as per their phytochemical nature. Furthermore, important key points along with important structure-activity relationships points regarding selected lead molecules are also discussed.

Chemoresistance is one of the major hurdles in cancer treatment leading to recurrence of cancer and affects the overall survival of patients. Cancer chemoresistance can be associated with various phenomena including modulation of vital cellular pathways. Unrevealing these alterations could provide a better understanding of chemoresistance and assist in the identification of new targets to overcome it. Recent advances in the field of proteomics and metabolomics have substantially helped in the identification of potential targets for chemoresistance in various cancers. This review highlights the potential of proteomics and metabolomics research to explore the putative targets associated with cancer chemoresistance with a special focus on Multiple Myeloma (MM). MM is a type of hematological malignancy which constitutes about 13% of all blood cell cancers. The therapeutic advancements for MM have increased the median overall survival rate to over 3-fold in the last one and half decade. Although in recent times, significant improvements in the overall survival rate of MM are achieved, MM remains an incurable disease with unpredictable refractory mechanisms. In spite of therapeutic advances, chemoresistance thrives to be a major hurdle in the treatment of multiple myeloma which demands a better understanding of chemoresistance. In this review, we have attempted to highlight the potential applications of proteomics and metabolomics research in the understanding of chemoresistance in MM.

Autophagy is an intracellular biological catabolic process of mammalian cells to maintain the homeostasis. It plays a wide role in the clearance of damaged cellular organelles, misfolded or aggregated proteins like alpha-synuclein, β-amyloid peptides, Tau proteins and pathogens. Recent studies have clearly demonstrated that dysfunction in autophagy leads to the development of cancer, cardiomyopathy, chronic infection, neurodegenerative and other diseases. Therefore, modulation of autophagy has therapeutic value to cure the diseases including cancer using external stimuli. In this context, various researchers developed small molecules such as chloroquine, rapamycin, etc. for the treatment of cancer through autophagy. However, these molecules possess side effects which limit their use in the clinics. Therefore, nanomedicine approach could stand as an alternative treatment option to induce the autophagy in cancer therapy. Several investigators developed a variety of nanomaterials which themselves act as autophagy inducers or inhibitors. Considering this, the present review article will focus on the recent developments of nanomedicine in the area of autophagy that have been focused on the treatment of cancers. We also summarised the detailed mechanisms of nanoparticles mediated autophagy which could be helpful for developing new strategies to fight against cancer. Also, the present review article covers the current clinical status of nanomedicine and future challenges. Finally, we conclude with the future potential role of nanomedicine for autophagy induction in the cancer treatment.

Colorectal cancer (CRC) is a heterogeneous malignancy leading to increased mortality and poor prognosis due to the lack of efficient early diagnostics. Metastasis of the tumor being the most common cause of mortality is accountable for almost 90% of CRC associated deaths. Intensified screening procedures and molecular target identification has inflated the median survival rate of in CRC patients. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have come forward as potential targets for developing a novel approach in CRC theragnostics. Non-coding RNA (ncRNAs) sequences are abundantly present and thereby play a vital role in several biological processes such as cellular organization, cell fate determination, proliferation, apoptosis, tissue homeostasis maintenance as well as pathological conditions such as cancer by acting as post transcriptional regulators of gene expression. Several studies have highlighted the involvement of these ncRNAs in CRC development. However, the molecular mechanism involved in regulating CRC has not been clearly elucidated. This review, throws light upon the several non-coding RNAs involved in CRC with a focus on novel mechanisms of action, recent advances in the regulatory mechanisms that control the gene expression related to carcinogenesis. Furthermore, the potential role of ncRNAs as diagnostic as well as therapeutic targets has been reviewed.