Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 13, 2022

Regulated cell death (RCD), also well-known as programmed (PCD), refers to the form of that can be regulated by a variety biomacromolecules, which is distinctive from accidental (ACD). Accumulating evidence has revealed RCD subroutines are key features tumorigenesis, may ultimately lead establishment different potential therapeutic strategies. Hitherto, targeting with pharmacological small-molecule compounds been emerging promising avenue, rapidly progressed in many types human cancers. Thus, this review, we focus on summarizing not only apoptotic and autophagy-dependent signaling pathways, but crucial pathways other subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis lysosome-dependent (LCD) cancer. Moreover, further discuss current situation several improve cancer treatment, such single-target, dual or multiple-target compounds, drug combinations, some new strategies would together shed light future directions attack vulnerabilities drugs for purposes.

Language: Английский

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Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer

Pharmacological Research, Journal Year: 2021, Volume and Issue: 171, P. 105759 - 105759

Published: July 8, 2021

Language: Английский

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Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: April 12, 2022

Abstract Triple-negative breast cancer (TNBC) is a subtype of human with one the worst prognoses, no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed (PCD), has been widely reported to have numerous links progression and therapy many types cancer. Of note, RCD can be divided into different subroutines, including autophagy-dependent death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis anoikis. More recently, targeting subroutines small-molecule compounds emerging promising strategy, which rapidly progressed in treatment TNBC. Therefore, this review, we focus on summarizing molecular mechanisms above-mentioned seven major related TNBC latest progress subroutines. Moreover, further discuss combined drug (e.g., narciclasine) or more drugs torin-1 chloroquine) achieve potential by regulating importantly, demonstrate several ONC201 NCT03733119) clinical trials. Taken together, these findings will provide clue illuminating actionable low-hanging-fruit druggable targets candidate for RCD-related therapies. Graphical abstract

Language: Английский

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The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 15, 2023

Adenosine monophosphate-activated protein kinase (AMPK) is a key metabolic sensor that pivotal for the maintenance of cellular energy homeostasis. AMPK contributes to diverse and physiological effects besides its fundamental role in glucose lipid metabolism. Aberrancy signaling one determining factors which lead development chronic diseases such as obesity, inflammation, diabetes, cancer. The activation downstream cascades orchestrate dynamic changes tumor bioenergetics. It well documented possesses suppressor context progression by modulating inflammatory pathways. In addition, plays central potentiating phenotypic functional reprogramming various classes immune cells reside microenvironment (TME). Furthermore, AMPK-mediated responses facilitate recruitment certain types TME, impedes development, progression, metastasis Thus, appears play an important regulation anti-tumor response regulating plasticity cells. effectuates modulation immunity via nutrient TME virtue molecular crosstalk with major checkpoints. Several studies including from our lab emphasize on anticancer several phytochemicals, are potential drug candidates. scope this review encompasses significance cancer metabolism influence drivers within special emphasis use phytochemicals target combat

Language: Английский

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Targeting mitochondria as a potential therapeutic strategy against chemoresistance in cancer

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 160, P. 114398 - 114398

Published: Feb. 9, 2023

The importance of mitochondria is not only limited to energy generation but also in several physical and chemical processes critical for cell survival. Mitochondria play an essential role cellular apoptosis, calcium ion transport metabolism. Mutation the nuclear mitochondrial genes, altered oncogenes/tumor suppressor deregulated signalling viability are major reasons cancer progression chemoresistance. development drug resistance patients a challenge treatment as resistant cells often more aggressive. numerous types exhibit deregulation function. increased biogenesis its dynamic alteration contribute developing resistance. Further, small subpopulation stem heterogeneous tumor primarily responsible chemoresistance has attribute dysfunction. This review highlights dysfunction through autophagy/mitophagy, stemness. Mitochondria-targeted therapeutic strategies might help reduce induced by various drugs.

Language: Английский

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The Role of Curcumin in Cancer: A Focus on the PI3K/Akt Pathway

Cancers, Journal Year: 2024, Volume and Issue: 16(8), P. 1554 - 1554

Published: April 18, 2024

Cancer is a life-threatening disease and one of the leading causes death worldwide. Despite significant advancements in therapeutic options, most available anti-cancer agents have limited efficacy. In this context, natural compounds with diverse chemical structures been investigated for their multimodal properties. Curcumin polyphenol isolated from rhizomes Curcuma longa has widely studied its anti-inflammatory, anti-oxidant, effects. acts on regulation different aspects cancer development, including initiation, metastasis, angiogenesis, progression. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway key target therapy, since it implicated proliferation, cell survival. found to inhibit PI3K/Akt tumor cells, primarily via mediators, growth factors, protein kinases, cytokines. This review presents potential curcumin malignancies, such as glioblastoma, prostate breast cancer, head neck cancers, through targeting signaling pathway.

Language: Английский

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Sestrin2: multifaceted functions, molecular basis, and its implications in liver diseases

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 25, 2023

Abstract Sestrin2 (SESN2), a highly conserved stress-responsive protein, can be triggered by various noxious stimuli, such as hypoxia, DNA damage, oxidative stress, endoplasmic reticulum (ER) and inflammation. Multiple transcription factors regulate SESN2 expression, including hypoxia-inducible factor 1 (HIF-1), p53, nuclear E2-related 2 (Nrf2), activating 4 (ATF4), ATF6, etc. Upon induction, generally leads to activation of adenosine monophosphate-activated protein kinase (AMPK) inhibition mechanistic target rapamycin complex (mTORC1). To maintain cellular homeostasis, its downstream molecules directly scavenge reactive oxygen species or indirectly influence the expression patterns key genes associated with redox, macroautophagy, mitophagy, ER apoptosis, synthesis, In liver diseases acute injury, fatty diseases, hepatic fibrosis, hepatocellular carcinoma (HCC), is abnormally expressed correlated disease progression. NAFLD, helps postponing progression through balancing glycolipid metabolism macroautophagy (lipophagy), rectifying damage stress. During represses HSCs intrahepatic inflammation, hindering occurrence progress fibrogenesis. However, role in HCC controversial due paradoxical pro-autophagic anti-apoptotic effects. conclusion, this review summarizes biological functions genotoxic specifically emphasizes pathophysiological significance aiming providing comprehensive understanding for potential therapeutic diseases.

Language: Английский

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Targeted intervention of natural medicinal active ingredients and traditional Chinese medicine on epigenetic modification: Possible strategies for prevention and treatment of atherosclerosis

Phytomedicine, Journal Year: 2023, Volume and Issue: 122, P. 155139 - 155139

Published: Oct. 6, 2023

Language: Английский

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Lysosomes as a Target of Anticancer Therapy

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2176 - 2176

Published: Jan. 22, 2023

Lysosomes are organelles containing acidic hydrolases that responsible for lysosomal degradation and the maintenance of cellular homeostasis. They play an important role in autophagy, as well various cell death pathways, such apoptotic death. Various agents, including drugs, can induce membrane permeability, resulting translocation into cytoplasm, which promotes lysosomal-mediated This type may be great importance anti-cancer therapy, both cancer cells with disturbed pathways leading to apoptosis drug-resistant undergo it. Important compounds damage include lysosomotropic compounds, antihistamines, immunosuppressants, DNA-damaging chemotherapeutics, photosensitizers plant compounds. An interesting approach treatment search ways overcome chemoresistance also combining targeted modulators autophagy These alternative oncological treatment, lysosomes become a promising therapeutic target many diseases, cancer. Understanding functional relationships between possibilities their regulation, relation normal cells, used develop new more effective anticancer therapies.

Language: Английский

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Galectins and galectin-mediated autophagy regulation: new insights into targeted cancer therapy

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Feb. 22, 2023

Abstract Galectins are animal lectins with specific affinity for galactosides via the conserved carbohydrate recognition domains. Increasing studies recently have identified critical roles of galectin family members in tumor progression. Abnormal expression galectins contributes to proliferation, metastasis, epithelial-mesenchymal transformation (EMT), immunosuppression, radio-resistance and chemoresistance various cancers, which has attracted cumulative clinical interest galectin-based cancer treatment. Galectin been reported participate autophagy regulation under physiological conditions non-tumoral diseases, implication multiple processes carcinogenesis also involves autophagy, however, relationship between galectins, remains largely unclear. In this review, we introduce structure function at molecular level, summarize their engagements progression, highlight by as well therapeutic potentials autophagy-based strategies. Elaborating on mechanism galectin-regulated cancers will accelerate exploitation galectins-autophagy targeted therapies treatment cancer.

Language: Английский

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