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This review presents current knowledge related to the voltage-dependent anion channel-1 (VDAC1) as a multi-functional mitochondrial protein that acts in regulating both cell life and death. The location of VDAC1 at the outer mitochondrial membrane (OMM) allows control of metabolic cross-talk between the mitochondria and the rest of the cell, and also enables its interaction with proteins that are involved in metabolic, cell death, and survival pathways. VDAC1's interactions with over 150 proteins can mediate and regulate the integration of mitochondrial functions with cellular activities. To target these protein-protein interactions, VDAC1-derived peptides have been developed. This review focuses specifically on cell-penetrating VDAC1-based peptides that were developed and used as a "decoy" to compete with VDAC1 for its VDAC1-interacting proteins. These peptides interfere with VDAC1 interactions, for example, with metabolism-associated proteins such as hexokinase (HK), or with anti-apoptotic proteins such as Bcl-2 and Bcl-xL. These and other VDAC1-interacting proteins are highly expressed in many cancers. The VDAC1-based peptides in cells in culture selectively affect cancerous, but not non-cancerous cells, inducing cell death in a variety of cancers, regardless of the cancer origin or genetics. They inhibit cell energy production, eliminate cancer stem cells, and act very rapidly and at low micro-molar concentrations. The activity of these peptides has been validated in several mouse cancer models of glioblastoma, lung, and breast cancers. Their anti-cancer activity involves a multi-pronged attack targeting the hallmarks of cancer. They were also found to be effective in treating non-alcoholic fatty liver disease and diabetes mellitus. Thus, VDAC1-based peptides, by targeting VDAC1-interacting proteins, offer an affordable and innovative new conceptual therapeutic paradigm that can potentially overcome heterogeneity, chemoresistance, and invasive metastatic formation.

The impact of kinetic lability or reactivity on in vitro cytotoxicity, stability in plasma, in vivo tumor and tissue accumulation, and antitumor efficacy of functional platinum(II) (Pt) anticancer agents containing a O˄O β-diketonate leaving ligand remain largely unexplored. To investigate this, we synthesized Pt complexes [(NH 3 ) 2 Pt(L1-H)]NO 3 and [(DACH)Pt(L1-H)]NO 3 (L1=4,4,4-trifluoro-1-ferrocenylbutane-1,3-dione, DACH=1R,2R-cyclohexane-1,2-diamine) containing an electron deficient [L1-H] - O˄O leaving ligand and [(NH 3 ) 2 Pt(L2-H)]NO 3 and [(DACH)Pt(L2-H)]NO 3 (L2=1-ferrocenylbutane-1,3-dione) containing an electron-rich [L2-H] - O˄O leaving ligand. While all four complexes have comparable lipophilicity, the presence of the electron-withdrawing CF 3 group was found to dramatically enhance the reactivity of these complexes toward nucleophilic biomolecules. In vitro cellular assays revealed that the more reactive complexes have higher cellular uptake and higher anticancer potency as compared to their less reactive analogs. But the scenario is opposite in vivo, where the less reactive complex showed improved tissue and tumor accumulation and better anticancer efficacy in mice bearing ovarian xenograft when compared to its more reactive analog. Finally, in addition to demonstrating the profound but contrasting impact of kinetic lability on in vitro and in vivo antitumor potencies, we also described the impact of kinetic lability on the mechanism of action of this class of promising antitumor agents., (© 2023 Wiley-VCH GmbH.)

Anticancer therapies have been the continual pursuit of this age. Cancer has been ravaging all across the globe breathing not just threats but demonstrating them. Remedies for cancer have been frantically sought after. Few have worked out, yet till date, the available cancer therapies have not delivered a holistic solution. In a world where the search for therapies is levitating towards natural remedies, solutions based on phytochemicals are highly prospective attractions. A lot has been achieved with inputs from plant resources, providing numerous natural remedies. In the current review, we intensely survey the progress achieved in the treatment of cancer through phytochemicals-based programmed cell death of cancer cells. More specifically, we have further reviewed and discussed the role of phytochemicals in activating apoptosis via Tumor Necrosis Factor-Alpha-Related Apoptosis-Inducing Ligand (TRAIL), which is a cell protein that can attach to certain molecules in cancer cells, killing cancer cells. The objective of this review is to enlist the various phytochemicals that are available for specifically contributing towards triggering the TRAIL cell protein-mediated cancer therapy and to point out the research gaps that require future research motivation. This is the first review of this kind in this research direction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Even in the modern era of precision medicine and immunotherapy, chemotherapy with platinum (Pt) drugs remains among the most commonly prescribed medications against a variety of cancers. Unfortunately, the broad applicability of these blockbuster Pt drugs is severely limited by intrinsic and/or acquired resistance, and high systemic toxicity. Considering the strong interconnection between kinetic lability and undesired shortcomings of clinical Pt drugs, we rationally designed kinetically inert organometallic Pt based anticancer agents with a novel mechanism of action. Using a combination of in vitro and in vivo assays, we demonstrated that the development of a remarkably efficacious but kinetically inert Pt anticancer agent is feasible. Along with exerting promising antitumor efficacy in Pt-sensitive as well as Pt-resistant tumors in vivo, our best candidate has the ability to mitigate the nephrotoxicity issue associated with cisplatin. In addition to demonstrating, for the first time, the power of kinetic inertness in improving the therapeutic benefits of Pt based anticancer therapy, we describe the detailed mechanism of action of our best kinetically inert antitumor agent. This study will certainly pave the way for designing the next generation of anticancer drugs for effective treatment of various cancers., (© 2023 Wiley-VCH GmbH.)

After decades of research and development concerning cancer treatment, cancer is still at large and very much a threat to the global human population. Cancer remedies have been sought from all possible directions, including chemicals, irradiation, nanomaterials, natural compounds, and the like. In this current review, we surveyed the milestones achieved by green tea catechins and what has been accomplished in cancer therapy. Specifically, we have assessed the synergistic anticarcinogenic effects when green tea catechins (GTCs) are combined with other antioxidant-rich natural compounds. Living in an age of inadequacies, combinatorial approaches are gaining momentum, and GTCs have progressed much, yet there are insufficiencies that can be improvised when combined with natural antioxidant compounds. This review highlights that there are not many reports in this specific area and encourages and recommends research attention in this direction. The antioxidant/prooxidant mechanisms of GTCs have also been highlighted. The current scenario and the future of such combinatorial approaches have been addressed, and the lacunae in this aspect have been discussed.

Of the biologically active components, polysaccharides play a crucial role of high medical and pharmaceutical significance. Mushrooms have existed for a long time, dating back to the time of the Ancient Egypt and continue to be well explored globally and experimented with in research as well as in national and international cuisines. Mushroom polysaccharides have slowly become valuable sources of nutraceuticals which have been able to treat various diseases and disorders in humans. The application of mushroom polysaccharides for anticancer mycotherapy is what is being reviewed herein. The widespread health benefits of mushroom polysaccharides have been highlighted and the significant inputs of mushroom-based polysaccharides in anticancer clinical trials have been presented. The challenges and limitation of mushroom polysaccharides into this application and the gaps in the current application areas that could be the future direction have been discussed.

Selenium (Se) is incorporated into the body via the selenocysteine (Sec) biosynthesis pathway, which is critical in the synthesis of selenoproteins, such as glutathione peroxidases and thioredoxin reductases. Selenoproteins, which play a key role in several biological processes, including ferroptosis, drug resistance, endoplasmic reticulum stress, and epigenetic processes, are guided by Se uptake. In this review, we critically analyze the molecular mechanisms of Se metabolism and its potential as a therapeutic target for cancer. Sec insertion sequence binding protein 2 (SECISBP2), which is a positive regulator for the expression of selenoproteins, would be a novel prognostic predictor and an alternate target for cancer. We highlight strategies that attempt to develop a novel Se metabolism-based approach to uncover a new metabolic drug target for cancer therapy. Moreover, we expect extensive clinical use of SECISBP2 as a specific biomarker in cancer therapy in the near future. Of note, scientists face additional challenges in conducting successful research, including investigations on anticancer peptides to target SECISBP2 intracellular protein., (© 2021 Wiley Periodicals LLC.)

Inhibitors of the mitotic kinase PLK1 yield objective responses in a subset of refractory cancers. However, PLK1 overexpression in cancer does not correlate with drug sensitivity, and the clinical development of PLK1 inhibitors has been hampered by the lack of patient selection marker. Using a high-throughput chemical screen, we discovered that cells deficient for the tumor suppressor ARID1A are highly sensitive to PLK1 inhibition. Interestingly this sensitivity was unrelated to canonical functions of PLK1 in mediating G2/M cell cycle transition. Instead, a whole-genome CRISPR screen revealed PLK1 inhibitor sensitivity in ARID1A deficient cells to be dependent on the mitochondrial translation machinery. We find that ARID1A knock-out (KO) cells have an unusual mitochondrial phenotype with aberrant biogenesis, increased oxygen consumption/expression of oxidative phosphorylation genes, but without increased ATP production. Using expansion microscopy and biochemical fractionation, we see that a subset of PLK1 localizes to the mitochondria in interphase cells. Inhibition of PLK1 in ARID1A KO cells further uncouples oxygen consumption from ATP production, with subsequent membrane depolarization and apoptosis. Knockdown of specific subunits of the mitochondrial ribosome reverses PLK1-inhibitor induced apoptosis in ARID1A deficient cells, confirming specificity of the phenotype. Together, these findings highlight a novel interphase role for PLK1 in maintaining mitochondrial fitness under metabolic stress, and a strategy for therapeutic use of PLK1 inhibitors. To translate these findings, we describe a quantitative microscopy assay for assessment of ARID1A protein loss, which could offer a novel patient selection strategy for the clinical development of PLK1 inhibitors in cancer., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

The tumor microenvironment is immunosuppressive. Here we preview two recent studies from Ma et al. (2021) in Cell Metabolism and Xu et al. (2021) in Immunity that describe a key role of T cell-expressed CD36 in enhancing lipid uptake and mediating lipid peroxidation that ultimately leads to CD8+ T cell dysfunction, ferroptosis, and reduced anti-tumor function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Nimbolide, a major limonoid constituent of Azadirachta indica , commonly known as neem, has attracted increasing research attention owing to its wide spectrum of pharmacological properties, predominantly anticancer activity. Nimbolide is reported to exert potent antiproliferative effects on a myriad cancer cell lines and chemotherapeutic efficacy in preclinical animal tumor models. The potentiality of nimbolide to circumvent multidrug resistance and aid in targeted protein degradation broaden its utility in enhancing therapeutic modalities and outcome. Accumulating evidence indicates that nimbolide prevents the acquisition of cancer hallmarks such as sustained proliferation, apoptosis evasion, invasion, angiogenesis, metastasis, and inflammation by modulating kinase-driven oncogenic signaling networks. Nimbolide has been demonstrated to abrogate aberrant activation of cellular signaling by influencing the subcellular localization of transcription factors and phosphorylation of kinases in addition to influencing the epigenome. Nimbolide, with its ever-expanding repertoire of molecular targets, is a valuable addition to the anticancer drug arsenal.

Crowded outpatient clinics and common wards in many hospitals in low and middle-income countries predispose children, caregivers, and health care workers to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on the clinical features and outcomes of 15 children with cancer at our center who tested positive for SARS-CoV-2. Five out of 15 patients were symptomatic, and one patient required intensive care and respiratory support. All the patients in the study have recovered from the SARS-CoV-2 infection without any sequelae and have resumed their cancer treatment.

The mutagenic APOBEC3B (A3B) cytosine deaminase is frequently over-expressed in cancer and promotes tumour heterogeneity and therapy resistance. Hence, understanding the mechanisms that underlie A3B over-expression is important, especially for developing therapeutic approaches to reducing A3B levels, and consequently limiting cancer mutagenesis. We previously demonstrated that A3B is repressed by p53 and p53 mutation increases A3B expression. Here, we investigate A3B expression upon treatment with chemotherapeutic drugs that activate p53, including 5-fluorouracil, etoposide and cisplatin. Contrary to expectation, these drugs induced A3B expression and concomitant cellular cytosine deaminase activity. A3B induction was p53-independent, as chemotherapy drugs stimulated A3B expression in p53 mutant cells. These drugs commonly activate ATM, ATR and DNA-PKcs. Using specific inhibitors and gene knockdowns, we show that activation of DNA-PKcs and ATM by chemotherapeutic drugs promotes NF-κB activity, with consequent recruitment of NF-κB to the A3B gene promoter to drive A3B expression. Further, we find that A3B knockdown re-sensitises resistant cells to cisplatin, and A3B knockout enhances sensitivity to chemotherapy drugs. Our data highlight a role for A3B in resistance to chemotherapy and indicate that stimulation of A3B expression by activation of DNA repair and NF-κB pathways could promote cancer mutations and expedite chemoresistance.

Obesity is growing at an alarming rate, which is characterized by increased adipose tissue. It increases the probability of many health complications, such as diabetes, arthritis, cardiac disease, and cancer. In modern society, with a growing population of obese patients, several individuals have increased insulin resistance. Herbal medicines are known as the oldest method of health care treatment for obesity-related secondary health issues. Several traditional medicinal plants and their effective phytoconstituents have shown anti-diabetic and anti-adipogenic activity. Adipose tissue is a major site for lipid accumulation as well as the whole-body insulin sensitivity region. 3T3-L1 cell line model can achieve adipogenesis. Adipocyte characteristics features such as expression of adipocyte markers and aggregation of lipids are chemically induced in the 3T3-L1 fibroblast cell line. Differentiation of 3T3-L1 is an efficient and convenient way to obtain adipocyte like cells in experimental studies. Peroxisome proliferation activated receptor γ (PPARγ) and Cytosine-Cytosine-Adenosine-Adenosine-Thymidine/Enhancer-binding protein α (CCAAT/Enhancer-binding protein α or C/EBPα) are considered to be regulating adipogenesis at the early stage, while adiponectin and fatty acid synthase (FAS) is responsible for the mature adipocyte formation. Excess accumulation of these adipose tissues and lipids leads to obesity. Thus, investigating adipose tissue development and the underlying molecular mechanism is important in the therapeutical approach. This review describes the cellular mechanism of 3T3-L1 fibroblast cells on potential anti-adipogenic herbal bioactive compounds.

Glycosylation plays a crucial role in various diseases and their etiology. This has led to a clear understanding on the functions of carbohydrates in cell communication, which eventually will result in novel therapeutic approaches for treatment of various disease. Glycomics has now become one among the top ten technologies that will change the future. The direct implication of glycosylation as a hallmark of cancer and for cancer therapy is well established. As in proteomics, where bioinformatics tools have led to revolutionary achievements, bioinformatics resources for glycosylation have improved its practical implication. Bioinformatics tools, algorithms and databases are a mandatory requirement to manage and successfully analyze large amount of glycobiological data generated from glycosylation studies. This review consolidates all the available tools and their applications in glycosylation research. The achievements made through the use of bioinformatics into glycosylation studies are also presented. The importance of glycosylation in cancer diagnosis and therapy is discussed and the gap in the application of widely available glyco-informatic tools for cancer research is highlighted. This review is expected to bring an awakening amongst glyco-informaticians as well as cancer biologists to bridge this gap, to exploit the available glyco-informatic tools for cancer.

Background: Breakthrough chemotherapy-induced vomiting (CIV) is defined as CIV occurring after adequate antiemetic prophylaxis. Olanzapine and metoclopramide are two drugs recommended for the treatment of breakthrough CIV in children, without adequate evidence. We conducted an open-label, single-center, phase 3 randomized controlled trial comparing the safety and efficacy of olanzapine and metoclopramide for treating breakthrough CIV., Procedure: Children aged 5-18 years who developed breakthrough CIV after receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy were randomly assigned to the metoclopramide or olanzapine arm. The primary objective of the study was to compare the complete response (CR) rates between patients receiving olanzapine or metoclopramide for treating breakthrough CIV during 72 hours after the administration of the study drug. Secondary objectives were to compare CR rates for nausea and toxicities between the two arms., Results: Eighty patients were analyzed (39 in the olanzapine arm and 41 in the metoclopramide arm). CR rates were significantly higher in the olanzapine arm compared with the metoclopramide arm for vomiting (72% vs 39%, P = 0.003) and nausea (59% vs 34%, P = 0.026). Seven patients in the metoclopramide arm crossed over to the olanzapine arm and none crossed over in the olanzapine arm (P < 0.001). The mean nausea score in the olanzapine arm was significantly lower than the metoclopramide arm after the initiation of the rescue antiemetic (P = 0.01). Hyperglycemia and drowsiness were more commonly seen in the olanzapine arm., Conclusion: Olanzapine is superior to metoclopramide for the treatment of breakthrough CIV in children. Drowsiness and hyperglycemia need to be monitored closely in children receiving olanzapine for breakthrough CIV., (© 2020 Wiley Periodicals LLC.)

Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer cells using pro-apoptotic proteins. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Mu-2/AP1M2 domain containing, death-inducing (MUDENG, MuD) have been established for their ability to bring about cell death specifically in cancer cells. Targeted cell death is a very attractive term when it comes to cancer, since most therapies also affect normal cells. In this direction TRAIL has made noteworthy progress. This review briefly sums up what has been done using TRAIL in cancer therapeutics. The importance of MuD and what has been achieved thus far through MuD and the need to widen and concentrate on applicational aspects of MuD has been highlighted. This has been suggested as the future perspective of MuD towards prospective progress in cancer research.

Endothelial cell (EC) recruitment is central to the vascularization of tumors. Although several proteoglycans have been implicated in cancer and angiogenesis, their roles in EC recruitment and vascularization during tumorigenesis remain poorly understood. Here, we reveal that Agrin, which is secreted in liver cancer, promotes angiogenesis by recruiting ECs within tumors and metastatic lesions and facilitates adhesion of cancer cells to ECs. In ECs, Agrin-induced angiogenesis and adherence to cancer cells are mediated by Integrin-β1, Lrp4-MuSK pathways involving focal adhesion kinase. Mechanistically, we uncover that Agrin regulates VEGFR2 levels that sustain the angiogenic property of ECs and adherence to cancer cells. Agrin attributes an ECM stiffness-based stabilization of VEGFR2 by enhancing interactions with Integrin-β1-Lrp4 and additionally stimulates endothelial nitric-oxide synthase (e-NOS) signaling. Therefore, we propose that cross-talk between Agrin-expressing cancer and ECs favor angiogenesis by sustaining the VEGFR2 pathway., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Fosaprepitant is a neurokinin-1 receptor antagonist, approved for the prevention of chemotherapy-induced nausea and vomiting. The data on the use of fosaprepitant in children are limited and therefore we conducted a phase III randomized controlled trial., Procedure: Children aged 1-12 years scheduled to receive moderately or highly emetogenic chemotherapy were randomly assigned to arm-A (fosaprepitant) or arm-B (placebo). Children recruited to arm-A received intravenous ondansetron plus dexamethasone followed by fosaprepitant infusion. Children recruited to arm-B received the same drugs as those given to children in arm-A, except that fosaprepitant was substituted with a placebo. Ondansetron and dexamethasone were continued for 48 hours after completion of chemotherapy. The primary end point of the study was to determine the proportion of patients who achieved a complete response (CR), defined as no vomiting, no retching, and no use of rescue medication, during the 24-120 hours (delayed phase) after administration of the last dose of chemotherapy. Secondary end points were the proportion of patients who achieved a CR during the acute phase (0-24 hours) and overall after administration of the last dose of chemotherapy., Results: One-hundred-sixty-three patients were analyzed (81 in the fosaprepitant arm and 82 in the placebo arm). CR rates were significantly higher in the fosaprepitant arm compared to those in the placebo arm during the acute phase (86% vs 60%, P < 0.001), delayed phase (79% vs 51%, P < 0.001), and overall phase (70% vs 41%, P < 0.001). Three (4%) patients in the fosaprepitant arm and sixteen (20%) in the placebo arm required rescue anti-emetics (P = 0.0017)., Conclusion: Addition of fosaprepitant to ondansetron and dexamethasone improved chemotherapy-induced vomiting control in children treated with moderately or highly emetogenic chemotherapy., (© 2018 Wiley Periodicals, Inc.)

Cancer-related fatigue is a symptom of cancer where most patients or the general practitioners tend to misinterpret due to the insufficient understanding or knowledge of cancer-related fatigue (CRF). This paper will provide a better perspective for the patients and the health professionals on how to manage and handle CRF for both mild and severe fatigue patients. Articles were selected from the searches of PubMed database that had the terms "randomized controlled trials," "cancer," "fatigue," "pharmacologic treatment," and "nonpharmacologic treatment" using both Mesh terms and keywords. The authors have reviewed the current hypothesis and evidence of the detailed etiology of the CRF present in the literature for healthier management, directives, and strategies to improve the treatment of cancer-related fatigue. An algorithm has been blueprinted on screening, and management, of the CRF, and various kinds of effective treatments and assessment tools have been briefly studied and explained. Although many strategies seemed promising, the quality of randomized controlled trials is generally quite low in studies, making it difficult to draw conclusions about the effectiveness of each self-care strategies. Therefore, future studies require better design and reporting of methodological issues to ensure evidence-based self-care recommendations for people receiving cancer treatment.

We developed a cancer chip by nano-patterning a highly sensitive SAM titanium surface capable of capturing and sensing concentrations as low as 10 cancer cells/mL from the environment by Matrix Assisted Laser Desorption and Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). The current approach evades any form of pretreatment and sample preparation processes; it is time saving and does not require the (expensive) conventional MALDI target plate. The home made aluminium (Al) target holder cost, on which we loaded the cancer chips for MALDI-TOF MS analysis, is about 60 USD. While the conventional stainless steel MALDI target plate is more than 700 USD. The SAM surface was an effective platform leading to on-chip direct MALDI-MS detection of cancer cells. We compared the functionality of this chip with the unmodified titanium surfaces and thermally oxidized (TO) titanium surfaces. The lowest detectable concentration of the TO chip was 10(3) cells/mL, while the lowest detectable concentration of the control or unmodified titanium chips was 10(6) cells/mL. Compared to the control surface, the SAM cancer chip showed 100,000 times of enhanced sensitivity and compared with the TO chip, 1000 times of increased sensitivity. The high sensitivity of the SAM surfaces is attributed to the presence of the rutile SAM, surface roughness and surface wettability as confirmed by AFM, XRD, contact angle microscope and FE-SEM. This study opens a new avenue for the potent application of the SAM cancer chip for direct cancer diagnosis by MALDI-TOF MS in the near future., (Copyright © 2014. Published by Elsevier B.V.)

Cancer, a complex genetic disease involving uncontrolled cell proliferation, is caused by inactivation of tumor suppressor genes and activation of oncogenes. A vast majority of these cancer causing genes are known targets of microRNAs (miRNAs) that bind to complementary sequences in 3' untranslated regions (UTR) of messenger RNAs and repress them from translation. Single Nucleotide Polymorphisms (SNPs) occurring naturally in such miRNA binding regions can alter the miRNA:mRNA interaction and can significantly affect gene expression. We hypothesized that 3'UTR SNPs in miRNA binding sites of proto-oncogenes could abrogate their post-transcriptional regulation, resulting in overexpression of oncogenic proteins, tumor initiation, progression, and modulation of drug response in cancer patients. Therefore, we developed a systematic computational pipeline that integrates data from well-established databases, followed stringent selection criteria and identified a panel of 30 high-confidence SNPs that may impair miRNA target sites in the 3' UTR of 54 mRNA transcripts of 24 proto-oncogenes. Further, 8 SNPs amidst them had the potential to determine therapeutic outcome in cancer patients. Functional annotation suggested that altogether these SNPs occur in proto-oncogenes enriched for kinase activities. We provide detailed in silico evidence for the functional effect of these candidate SNPs in various types of cancer.

Background: The ubiquitin-proteasomal degradation pathway plays a critical role in protein degradation and regulates a wide variety of cellular functions. This highly conserved post-translational modification of proteolytic processes is mainly carried out by substrate-specific E3 ligases. The deregulation of E3 ligases contributes to cancer development and their overexpression is often associated with poor prognosis., Objectives: We review the current understanding of E3 ligases, their functional role in cancer pathogenesis, current progress and development of certain ubiquitin E3 ligases as targets for therapeutic intervention., Methods: Preclinical and clinical data for E3 ligase inhibitors available in the public domain are discussed., Conclusions: With the growing understanding of their role in cancer development and progression, E3 ligases have emerged as potential anticancer targets for therapeutic intervention.

Aurora kinases (AKs) represent a family of serine/threonine protein kinases that regulate mitotic processes during cell division. They are primarily involved in regulating the multiple steps of mitosis, including centrosome duplication, formation of bipolar mitotic spindle, chromosome alignment on the mitotic spindle, establishment and maintenance of the spindle checkpoint and cytokinesis. As AKs are key regulators of mitosis, several studies have indicated that they have a strong association with cancer and are overexpressed in numerous cancerous cell lines as well as human malignancies. Thus, AKs represent a promising therapeutic target for anticancer drug development. In this review, the role of AKs in cancer, and the current status and therapeutic potential of AK inhibitors is discussed.