Unveiling the mechanisms and challenges of cancer drug resistance

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Language: Английский

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The mechanism of ferroptosis and its related diseases

Molecular Biomedicine, Journal Year: 2023, Volume and Issue: 4(1)

Published: Oct. 16, 2023

Abstract Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation lipid peroxides, provides novel avenue for delving into intersection metabolism, oxidative stress, and disease pathology. We have witnessed mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, traumatic tissue injuries. By unraveling intricate underpinnings molecular machinery, contributors, signaling conduits, regulatory networks governing researchers aim bridge gap between intricacies this unique mode multifaceted implications health disease. In light rapidly advancing landscape ferroptosis research, we present comprehensive review aiming at extensive in origins progress human diseases. This concludes careful analysis potential treatment approaches carefully designed either inhibit or promote ferroptosis. Additionally, succinctly summarized therapeutic targets compounds that hold promise targeting within various facet underscores burgeoning possibilities manipulating as strategy. summary, enriched insights both investigators practitioners, while fostering an elevated comprehension latent translational utilities. revealing basic processes investigating possibilities, crucial resource scientists medical aiding deep understanding effects situations.

Language: Английский

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Mammalian SWI/SNF chromatin remodeling complexes promote tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(8), P. 1516 - 1534.e9

Published: Aug. 1, 2023

Acquired resistance to tyrosine kinase inhibitors (TKI), such as osimertinib used treat EGFR-mutant lung adenocarcinomas, limits long-term efficacy and is frequently caused by non-genetic mechanisms. Here, we define the chromatin accessibility gene regulatory signatures of sensitive resistant cell patient-derived models uncover a role for mammalian SWI/SNF remodeling complexes in TKI resistance. By profiling mSWI/SNF genome-wide localization, identify both shared cancer line-specific targets underlying state. Importantly, genetic pharmacologic disruption SMARCA4/SMARCA2 ATPases re-sensitizes subset via inhibition mSWI/SNF-mediated regulation cellular programs governing proliferation, epithelial-to-mesenchymal transition, epithelial differentiation, NRF2 signaling. These data highlight supporting suggest potential utility TKI-resistant cancers.

Language: Английский

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Mechanisms of Acquired Resistance and Tolerance to EGFR Targeted Therapy in Non-Small Cell Lung Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(2), P. 504 - 504

Published: Jan. 13, 2023

Non-small cell lung cancers (NSCLC) harboring activating mutations of the epidermal growth factor receptor (EGFR) are treated with specific tyrosine kinase inhibitors (EGFR-TKIs) this receptor, resulting in clinically responses that can generally last several months. Unfortunately, EGFR-targeted therapy also favors emergence drug tolerant or resistant cells, ultimately tumor relapse. Recently, cellular barcoding strategies have arisen as a powerful tool to investigate clonal evolution these subpopulations response anti-cancer drugs. In review, we provide an overview currently available treatment options for NSCLC, focusing on EGFR targeted therapy, and discuss common mechanisms resistance EGFR-TKIs. We review characteristics drug-tolerant persister (DTP) cells mechanistic basis tolerance EGFR-mutant NSCLC. Lastly, address how be applied behavior DTP upon EGFR-TKI treatment.

Language: Английский

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Dormancy, stemness, and therapy resistance: interconnected players in cancer evolution

Cancer and Metastasis Reviews, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 9, 2023

Abstract The biological complexity of cancer represents a tremendous clinical challenge, resulting in the frequent failure current treatment protocols. In rapidly evolving scenario growing tumor, anticancer treatments impose drastic perturbation not only to cells but also tumor microenvironment, killing portion and inducing massive stress response survivors. Consequently, can act as double-edged sword by temporary while laying ground for therapy resistance subsequent disease progression. Cancer cell dormancy (or quiescence) is central theme evolution, being tightly linked tumor’s ability survive cytotoxic challenges, metastasize, resist immune-mediated attack. Accordingly, quiescent (QCCs) have been detected virtually all stages development. recent years, an increasing number studies focused on characterization quiescent/therapy resistant cells, unveiling QCCs core transcriptional programs, metabolic plasticity, mechanisms immune escape. At same time, our partial understanding quiescence reflects difficulty identify stable biomarkers/therapeutic targets control settings. This review focuses discoveries interrelated fields dormancy, stemness, resistance, discussing experimental evidences frame nonlinear dynamics approach, exploring possibility that may represent peril potential therapeutic resource.

Language: Английский

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Ferroptotic therapy in cancer: benefits, side effects, and risks

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 3, 2024

Abstract Ferroptosis is a type of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture intracellular content release. Originally investigated as targeted therapy for cancer cells carrying oncogenic RAS mutations, ferroptosis induction now exhibits potential complement chemotherapy, immunotherapy, radiotherapy in various types. However, it can lead side effects, including immune death, bone marrow impairment, liver kidney damage, cachexia (severe weight loss muscle wasting), secondary tumorigenesis. In this review, we discuss the advantages offer an overview diverse range documented effects. Furthermore, examine underlying mechanisms explore strategies effect mitigation.

Language: Английский

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PINK1-Mediated Mitophagy Promotes Oxidative Phosphorylation and Redox Homeostasis to Induce Drug-Tolerant Persister Cancer Cells

Cancer Research, Journal Year: 2022, Volume and Issue: 83(3), P. 398 - 413

Published: Dec. 8, 2022

The drug-tolerant persister (DTP) state enables cancer cells to evade cytotoxic stress from anticancer therapy. However, the mechanisms governing DTP generation remain poorly understood. Here, we observed that lung adenocarcinoma (LUAD) and organoids entered a quiescent survive MAPK inhibitor treatment. following inhibition underwent metabolic switch glycolysis oxidative phosphorylation (OXPHOS). PTEN-induced kinase 1 (PINK1), serine/threonine initiates mitophagy, was upregulated maintain mitochondrial homeostasis during generation. PINK1-mediated mitophagy supported cell survival contributed poor prognosis. Mechanistically, pathway resulted in MYC-dependent transcriptional upregulation of PINK1, leading activation. Mitophagy using either clinically applicable chloroquine or depletion PINK1 eradicated drug tolerance allowed complete response inhibitors. This study uncovers as novel tumor protective mechanism for generation, providing therapeutic opportunity eradicate achieve responses.DTP cause relapse after therapy critically depend on reprogramming, prolong treatment efficacy.

Language: Английский

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Engineering defected 2D Pd/H-TiO2 nanosonosensitizers for hypoxia alleviation and enhanced sono-chemodynamic cancer nanotherapy

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: April 12, 2022

Sonodynamic therapy (SDT) is a burgeoning modality for cancer owing to its high tissue-penetrating capability, controllability and safety. Whereas, the undesirable reactive oxygen species (ROS) yield of sonosensitizers tumor hypoxia are two vulnerable spots SDT. Therefore, it an advisable strategy augment ROS level simultaneously relieve SDT arrive full potential in treatment.In this work, defected two-dimensional (2D) Pd/H-TiO2 nanosheets (NSs) with triple antineoplastic properties were dexterously elaborated engineered using facile one-pot Pd-catalyzed hydrogenation tactic by loading tiny amount Pd then inletting hydrogen flow at atmospheric pressure temperature. The 2D black NSs defects exerted eximious effect based on decreased bandgap that made easier separation electrons holes when triggered ultrasound as theoretically guided density functional theory calculations. Additionally, could serve Fenton-like agents because presence defects, facilitating conversion peroxide into hydroxyl radicals exerting chemodynamic (CDT). Simultaneously, introduced component possessed catalase-like activity responsible production ameliorate hypoxic condition thus contributed improving CDT efficacies. Both vitro vivo results provided compelling evidences aggrandized sono-chemodynamic nanosonosensitizers detailed underlying mechanism investigation RNA sequencing.This work delves profound hydrogenated TiO2 oncotherapy, effective performance ignorable therapeutic toxicity make powerful competitor among cornucopia nanosonosensitizers.

Language: Английский

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Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer

Cancer Research and Treatment, Journal Year: 2022, Volume and Issue: 54(2), P. 315 - 329

Published: Feb. 18, 2022

Precision oncology has fundamentally changed how we diagnose and treat cancer. In recent years, there been a significant change in the management of patients with oncogene-addicted advanced-stage NSCLC. Increasing amounts identifiable oncogene drivers have led to development molecularly targeted drugs. Undoubtedly, future thoracic is shifting toward increased molecular testing use therapies. For most part, these novel drugs proven be safe effective. As all great innovations, therapies pose unique challenges. Drug toxicities, resistance, access, costs are some expected obstacles that will need addressed. This review highlights major challenges NSCLC provides guidance for strategies.

Language: Английский

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Modulation of redox homeostasis: A strategy to overcome cancer drug resistance

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

Published: March 22, 2023

Cancer treatment is hampered by resistance to conventional therapeutic strategies, including chemotherapy, immunotherapy, and targeted therapy. Redox homeostasis manipulation one of the most effective innovative techniques for overcoming drug resistance. Reactive oxygen species (ROS), previously considered intracellular byproducts aerobic metabolism, are now known regulate multiple signaling pathways as second messengers. cells cope with elevated amounts ROS during therapy upregulating antioxidant system, enabling tumor via a variety mechanisms. In this review, we aim shed light on redox modification that may contribute We summarized molecular mechanisms which signaling-regulated resistance, altered efflux, action targets enhanced DNA damage repair, maintained stemness, reshaped microenvironment. A comprehensive understanding these interrelationships should improve efficacy from fundamental clinical research point view.

Language: Английский

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