Current Drug Targets - Volume 22, Issue 11, 2021

Over the past several years, remarkable progress towards the recognition of new therapeutic targets in tumor cells has led to the discovery and development of newer scaffolds of anti-tumor drugs. The exploration and exploitation of epigenetic regulation in tumor cells are of immense importance to both the pharmaceutical and academic biomedical literatures. Epigenetic mechanisms are indispensable for the normal development and maintenance of tissue-specific gene expression. Disruption of epigenetic processes to eradicate tumor cells is among the most promising intervention for cancer control. Polycomb repressive complex 2 (PRC2), a complex that methylates lysine 27 of histone H3 to promote transcriptional silencing, is involved in orchestrating significant pathways in a cell. Overexpression of PRC2 has been found in a number of cancerous malignancies, making it a major target for anti-cancer therapy. Despite its well-understood molecular mechanism, hyperactivation and drug resistance mutations in its subunits have become a matter of discussion. This review outlines the current understanding of the components of PRC2 in active complex formation and assesses their potential as a promising therapeutic target for cancer therapy. We also review the effects of mutations in the PRC2 components, in the purview of human cancers. Finally, we discuss some of the current challenges for therapeutic drug designs targeting the PRC2 complex.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is one of the leading causes of mortality worldwide, with an estimated 1.5 million deaths annually. The majority of infection cases are reported from the Southeast Asian region, including India. After the discovery of Streptomycin in 1943 and its anti-tubercular activity in 1945, drug discovery efforts identified Isoniazid, Ethambutol, and Rifampin as TB-actives. However, over the years, these drugs have been rendered ineffective due to genetic mutations in mycobacterial strains. This has shifted drug discovery efforts towards identifying new targets and drugs for drug-resistant forms of bacteria. ATP synthase was identified as one of the key targets of MDR-TB. This review provides key insights into the ATP synthase target, structure activity relationship studies (SAR) of diarylquinoline class of inhibitors and their clinical relevance for treating MDR-TB.

Gut microbiota is a complex microecosystem, which is called the second genome of the human body. Herbal medicine can balance tumor-suppressing bacteria and tumor-promoting bacteria and exert its anti-cancer effect by regulating gut microbiota. Traditional Chinese medicine (TCM) has a history of thousands of years in prevention and treatment of diseases in China. In recent decades, TCM has been shown to have an obvious advantage in prolonging the survival time and improving the living quality of patients with cancer. Notably, gut microbiota has become a new pathway to understanding TCM. In this review, we will focus on gut microbiota and tumor progression, especially the diversity, functionality and metabolites of gut microbiota affected by TCM in various cancer. We will also discuss the potential mechanism of gut microbiota for exploring TCM in anti-cancer effect. This article aims to comprehensively review the anti-cancer research of TCM by regulating gut microbiota, and address future perspectives and challenges of gut microbiota in TCM intervention for cancer.

Coronaviruses are a group of known RNA virus which primarily infect the respiratory tract, and also neurological, enteric, and hepatic systems. Endemic outbreaks of Middle East Coronavirus Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) have been observed in recent decades. A new strain named the SARS CoV-2(- COVID-19) virus has now spread across the globe. SARS-CoV-2 is highly communicable and has culminated in a massive pandemic of COVID-19. Currently, no successful treatment is available. Therefore, an urgent need is there for new screening models that can aid in identifying the drugs with potential activity against COVID-19. The current review aims to discuss various in-silico, in- -vitro and in-vivo screening methods that can potentially be used to expedite the discovery of new active therapeutic candidates and vaccines, drug targets, and repurposing the commercially available drugs against COVID-19 for the effective management of the infection and thereby controlling this pandemic. Further, the current status of drugs and vaccines under clinical investigation has been summarized.

Background: Breast cancer is the leading form of cancer in women, which is also hormone- dependent. Depending on the receptor expression, these cancers are subdivided into different forms, and among these receptors, estrogen, progesterone, and Her2 are the important ones. Targeting breast cancer (BC) has been difficult due to their varied nature; however, various phytocompounds, especially those having estrogen-like properties, have proven to be effective. Objective: The present review is aimed to provide a detailed description of various Phytocompounds inhibiting breast cancer proliferation and progression; emphasis has been given to the role of phytoestrogens with their molecular mechanism of action. Methods: The data were collected from reputed databases, such as PubMed/Medline, Web of Science, Science Direct, Eurekaselect, etc. Data on the phytoestrogens were collected using individual names and “phytoestrogens” as keywords. Articles published in journals, which are not indexed by Thomson Reuters (SCI/SCIE/ESCI), were omitted. Results: Natural products are important drug candidates against multiple forms of breast cancer. In addition to the initiation and proliferation events, these molecules inhibit epithelial to mesenchymal transition (EMT) and metastasis of BC. Phytoestrogens are an important class of compounds which have known estrogenic potential; studies have also indicated the anticancer potentials of these molecules in cell culture and animal models of BC. Conclusion: Natural plant compounds, especially phytoestrogens, are promising anti-breast cancer agents that induce cell cycle arrest, apoptosis, and autophagy-mediated cell death. However, more clinical studies are necessary so that these molecules can be used as commercial drug molecules.

Medicinal plants and mushrooms have always fascinated the world as an attractive source of natural compounds for cancer therapy. From ancient times, they have been valued as gourmet food and folk medicine in Oriental practice. For over 40 years, the world has witnessed the overwhelming interest of the western scientific fraternity in the pharmaceutical potential of natural products in combating cancer. The plants and mushrooms credited with success against angiogenesis and cancer metastasis belong to certain Plants, including Catharanthus roseus, Aloe Vera,Annona muricata,Curcuma longa, Withania somnifera, and Berberis and mushrooms such as Agaricus, Antrodia, Ganoderma, Grifolafrondosa, Hericiumerinaceus, Phellinuslinteus, and Trametesversicolor Coriolusversicolor. The anti-cancer compounds play a pivotal role as a free radical scavenger and reactive oxygen species inducer, mitotic spindle kinase inhibitor, anti-mitotic, angiogenesis inhibitor, topoisomerase inhibitor, apoptosis inducers, and eventually checking cancer invasion, migration and proliferation. The present review updates and focuses on the recent findings of the pharmacologically potential bioactive compounds, their anti-tumor potential, and underlying mechanism of preventing cancer metastasis and angiogenesis in order to raise knowledge for further investigations to develop cancer therapeutics with no adverse side effects The mounting experimental evidence at pre-clinical and clinical levels from various research groups across the globe, regarding prevention of cancer metastasis by natural products unarguably make it a fast-track research area worth mass attention.

Hepatocellular carcinoma (HCC) is one of the most common solid tumours and the second leading cause of cancer-related mortality worldwide. Advanced-recurrent HCC often requires a systemic drug therapy where multi tyrosine kinase inhibitor, Sorafenib represents the first-line therapy option. But it exhibited very limited survival benefit and tumour response due to the early emergence of drug resistance and drug-related adverse effect. Immunotherapy approaches now being widely studied as an effective alternative treatment for HCC. Several immune checkpoint inhibitors (ICI), such as Nivolumab and Pembrolizumab, are approved as monotherapy in sorafenib-resistant HCC patients. But, the existence of a plethora of immunosuppressive signals in the tumour microenvironment often leads to unsuccessful immunotherapies. In this context, combinatorial immunotherapies are getting much acceptance as a way to improve therapeutic outcomes by blocking immunosuppressive signals in the tumour microenvironment (TME). The combination of Vascular Endothelial Growth Factor (VEGF) inhibitors with ICI resulted in significant synergistic effects in various preclinical and clinical studies. However, the adverse effects associated with current synthetic VEGF inhibitors limit its clinical utility. In this review, we have summarized the potential of phytochemicals, especially the category of flavonoids, alkaloids, glycosides, terpenoids, and coumarin, as the available-affordable-safe-effective repositories of VEGF inhibitors. Their possibilities as an alternative for synthetic VEGF inhibitors by synergistic combination with ICI are reviewed, thereby enhancing patient compliance and survival rates. This review highlights the demand for a detailed investigation of the plausible role of plant-based anti-angiogenic-immunotherapy combination against HCC.

The regulatory mechanisms lying over the genome that determines the differential expression of genes are termed epigenetic mechanisms. DNA methylation, acetylation, and phosphorylation of histone proteins and RNAi are typical examples. These epigenetic modifications are important determinants of normal growth and metabolism; at the same time, aberrant histone modifications play a major role in pathological conditions and are emerging as a new area of research for the last decades. Histone onco-modification is a term introduced by the scientific world to denote histone post-translational modifications that are associated with cancer development and progression. These modifications are likely to act in certain conditions as adaptive mechanisms to environmental and social factors. The enzymes that regulate DNA methylation as well as histone modifications are thus become a target for cancer therapy and chemoprevention. Since oxidative stress has been shown to modulate epigenetic changes, and phytocompounds with powerful antioxidant properties have a significant role in disease prevention. Nowadays, “nutri- epigenetics” is becoming an emerging area of research that deals with the influence of dietary compounds in epigenetics. This review aims to discuss the biological efficacy of promising phytocompounds that are able to counteract deleterious epigenetic modifications, especially histone onco- modifications.