The Roles of ROS in Cancer Heterogeneity and Therapy

Oxidative Medicine and Cellular Longevity, Год журнала: 2017, Номер 2017(1)

Опубликована: Янв. 1, 2017

Cancer comprises a group of heterogeneous diseases encompassing high rates morbidity and mortality. Heterogeneity, which is hallmark cancer, one the main factors related to resistance chemotherapeutic agents leading poor prognosis. Heterogeneity profoundly affected by increasing levels ROS. Under low concentrations, ROS may function as signaling molecules favoring tumorigenesis heterogeneity, while under these species work cancer modulators due their deleterious, genotoxic or even proapoptotic effect on cells. This double‐edged sword represented relies ability cause genetic epigenetic modifications in DNA structure. Antitumor therapeutic approaches use that prevent formation precluding carcinogenesis chemical promote sudden increase causing considerable oxidative stress inside tumor mass. Therefore, herein, we review what are how they produced normal cells providing an argumentative discussion about role pathophysiology. We also describe various sources heterogeneity. Further, discuss some strategies from current landscape modulation, production.

Язык: Английский

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Perspectives on Triple-Negative Breast Cancer: Current Treatment Strategies, Unmet Needs, and Potential Targets for Future Therapies

Cancers, Год журнала: 2020, Номер 12(9), С. 2392 - 2392

Опубликована: Авг. 24, 2020

Triple-negative breast cancer (TNBC), characterized by the absence or low expression of estrogen receptor (ER), progesterone (PR), and human epidermal growth factor (HER2), is most aggressive subtype cancer. TNBC accounts for about 15% cases in U.S., known high relapse rates poor overall survival (OS). Chemo-resistant a genetically diverse, highly heterogeneous, rapidly evolving disease that challenges our ability to individualize treatment incomplete responders relapsed patients. Currently, frontline standard chemotherapy, composed anthracyclines, alkylating agents, taxanes, commonly used treat high-risk locally advanced TNBC. Several FDA-approved drugs target programmed cell death protein-1 (Keytruda) ligand-1 (Tecentriq), poly ADP-ribose polymerase (PARP), and/or antibody drug conjugates (Trodelvy) have shown promise improving clinical outcomes subset These inhibitors key genetic mutations specific molecular signaling pathways drive malignant tumor been as single agents combination with chemotherapy regimens. Here, we review current options, unmet needs, actionable targets, including (EGFR), vascular endothelial (VEGF), androgen (AR), beta (ERβ), phosphoinositide-3 kinase (PI3K), mammalian rapamycin (mTOR), protein B (PKB AKT) activation Supported strong evidence developmental, evolutionary, biology, propose K-RAS/SIAH pathway major driver, SIAH new target, therapy-responsive prognostic biomarker, vulnerability Since persistent K-RAS/SIAH/EGFR endows cells chemo-resistance, dissemination, early relapse, hope design an anti-SIAH-centered anti-K-RAS/EGFR targeted therapy novel therapeutic strategy control eradicate incurable future.

Язык: Английский

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Progesterone signalling in breast cancer: a neglected hormone coming into the limelight

Nature reviews. Cancer, Год журнала: 2013, Номер 13(6), С. 385 - 396

Опубликована: Май 24, 2013

Язык: Английский

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Epigenetic heterogeneity in cancer

Biomarker Research, Год журнала: 2019, Номер 7(1)

Опубликована: Окт. 31, 2019

Phenotypic and functional heterogeneity is one of the hallmarks human cancers. Tumor genotype variations among tumors within different patients are known as interpatient heterogeneity, variability multiple same type arising in patient referred to intra-patient heterogeneity. Subpopulations cancer cells with distinct phenotypic molecular features a tumor called intratumor (ITH). Since Nowell proposed clonal evolution cell populations 1976, especially ITH, was actively studied. Research has focused on genetic basis cancer, particularly mutational activation oncogenes or inactivation tumor-suppressor genes (TSGs). The phenomenon ITH commonly explained by Darwinian-like single tumor. Despite monoclonal origin most cancers, new clones arise during progression due continuous acquisition mutations. It clear that disruption "epigenetic machinery" plays an important role development. Aberrant epigenetic changes occur more frequently than gene mutations epigenome at intersection environment genome. Epigenetic dysregulation occurs earliest stage cancer. current trend therapy use drugs reverse and/or delay future resistance therapies. A majority therapies fail achieve durable responses, which often attributed ITH. may drug heterogeneous Complete understanding assist designing combinations targeted based information extracted from individual tumors.

Язык: Английский

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Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review

Nutrients, Год журнала: 2018, Номер 10(5), С. 645 - 645

Опубликована: Май 19, 2018

Novel and alternative options are being adopted to combat the initiation progression of human cancers. One approaches is use molecules isolated from traditional medicinal herbs, edible dietary plants seeds that play a pivotal role in prevention/treatment cancer, either alone or combination with existing chemotherapeutic agents. Compounds modulate these oncogenic processes potential candidates for cancer therapy may eventually make it clinical applications. Diosgenin naturally occurring steroidal sapogenin one major bioactive compounds found fenugreek (Trigonella foenum-graecum) seeds. In addition lactation aid, diosgenin has been shown be hypocholesterolemic, gastro- hepato-protective, anti-oxidant, anti-inflammatory, anti-diabetic, anti-cancer. unique structural similarity estrogen. Several preclinical studies have reported on pro-apoptotic anti-cancer properties against variety cancers, both vitro vivo. also reverse multi-drug resistance cells sensitize standard chemotherapy. Remarkably, used by pharmaceutical companies synthesize drugs. novel analogs nano-formulations synthesized improved efficacy pharmacokinetic profile. this review we discuss detail multifaceted application pharmaceutical, functional food, cosmetic industries; various intracellular molecular targets modulated abrogate process.

Язык: Английский

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