Unveiling the mechanisms and challenges of cancer drug resistance

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Фев. 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.

Язык: Английский

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Aging, oxidative stress and degenerative diseases: mechanisms, complications and emerging therapeutic strategies

Biogerontology, Год журнала: 2023, Номер 24(5), С. 609 - 662

Опубликована: Июль 30, 2023

Язык: Английский

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Ablation of Gap Junction Protein Improves the Efficiency of Nanozyme‐Mediated Catalytic/Starvation/Mild‐Temperature Photothermal Therapy

Advanced Materials, Год журнала: 2023, Номер 35(22)

Опубликована: Март 25, 2023

Reactive oxygen species (ROS)-mediated tumor catalytic therapy is typically hindered by gap junction proteins that form cell-to-cell channels to remove cytotoxic ROS, thereby protecting cells from oxidative damage. In this work, a multifunctional nanozyme, FePGOGA, designed and prepared Fe(III)-mediated polymerization (FeP), followed glucose oxidase (GOx) GAP19 peptides co-loading through electrostatic π-π interactions. The FePGOGA nanozyme exhibits excellent cascade peroxidase- glutathione-oxidase-like activities efficiently catalyze hydrogen peroxide conversion hydroxyl radicals convert reduced glutathione oxidized disulfide. loaded GOx starves the tumors aggravates stress decomposition, while block hemichannels inducing degradation of Cx43, thus increasing accumulation intracellular decreasing transport glucose. Furthermore, ROS reacts with primary amines heat shock destroy their structure function, enabling photothermal at widely sought-after mild temperature (mildPTT, ≤45 °C). vivo experiments demonstrate significant antitumor effectof on cal27 xenograft under near-infrared light irradiation. This study demonstrates successful ablation overcome resistance ROS-mediated therapy, providing regulator suppress self-preservation during starvation, mildPTT.

Язык: Английский

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A new wave of innovations within the DNA damage response

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 8, 2023

Genome instability has been identified as one of the enabling hallmarks in cancer. DNA damage response (DDR) network is responsible for maintenance genome integrity cells. As cancer cells frequently carry DDR gene deficiencies or suffer from replicative stress, targeting processes could induce excessive damages (or unrepaired DNA) that eventually lead to cell death. Poly (ADP-ribose) polymerase (PARP) inhibitors have brought impressive benefit patients with breast (BRCA) mutation homologous recombination deficiency (HRD), which proves concept synthetic lethality treatment. Moreover, other two scenarios inhibitor application, replication stress and combination chemo- radio- therapy, are under active clinical exploration. In this review, we revisited progress therapy beyond launched first-generation PARP inhibitors. Next generation PARP1 selective inhibitors, maintain efficacy while mitigating side effects, may diversify application clinic. Albeit unavoidable on-mechanism toxicities, several small molecules checkpoints (gatekeepers) shown great promise preliminary results, warrant further evaluations. addition, repair pathways (caretakers) also preclinical development. With these progresses efforts, envision a new wave innovations within come age.

Язык: Английский

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Genomic Instability and Epigenetic Changes during Aging

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(18), С. 14279 - 14279

Опубликована: Сен. 19, 2023

Aging is considered the deterioration of physiological functions along with an increased mortality rate. This scientific review focuses on central importance genomic instability during aging process, encompassing a range cellular and molecular changes that occur advancing age. In particular, this revision addresses genetic epigenetic alterations contribute to instability, such as telomere shortening, DNA damage accumulation, decreased repair capacity. Furthermore, explores aging, including modifications histones, methylation patterns, role non-coding RNAs. Finally, discusses organization chromatin its contribution heterochromatin loss, remodeling, in nucleosome histone abundance. conclusion, highlights fundamental plays process underscores need for continued research into these complex biological mechanisms.

Язык: Английский

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DNA Damage and Its Role in Cancer Therapeutics

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4741 - 4741

Опубликована: Март 1, 2023

DNA damage is a double-edged sword in cancer cells. On the one hand, exacerbates gene mutation frequency and risk. Mutations key repair genes, such as breast 1 (BRCA1) and/or 2 (BRCA2), induce genomic instability promote tumorigenesis. other induction of using chemical reagents or radiation kills cells effectively. Cancer-burdening mutations repair-related genes imply relatively high sensitivity to chemotherapy radiotherapy because reduced efficiency. Therefore, designing specific inhibitors targeting enzymes pathway an effective way synthetic lethality with therapeutics. This study reviews general pathways involved potential proteins that could be targeted for

Язык: Английский

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Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

Cancer Communications, Год журнала: 2024, Номер 44(3), С. 297 - 360

Опубликована: Фев. 4, 2024

Abstract Cancer is a leading cause of death worldwide. Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiotherapy as well immunotherapy have benefited cancer patients considerably. Tumor protein p53 ( TP53 ), crucial tumor suppressor gene encoding p53, regulates numerous downstream genes cellular phenotypes response to various stressors. The affected are involved diverse processes, including cell cycle arrest, DNA repair, senescence, metabolic homeostasis, apoptosis, autophagy. However, accumulating recent studies continued reveal novel unexpected functions governing the fate tumors, for example, ferroptosis, immunity, microenvironment microbiome metabolism. Among possibilities, evolutionary plasticity most controversial, partially due dizzying array biological that been attributed different regulatory mechanisms signaling. Nearly 40 years after its discovery, this remains somewhat enigmatic. intricate regulating during treatment only tip iceberg respect equally complicated structural biology, which has painstakingly revealed. Additionally, mutation one significant genetic alterations cancer, contributing rapid growth progression. Here, we summarized advances implicate altered modulating therapies, chemotherapy, radiotherapy, immunotherapy. Furthermore, also discussed potential strategies targeting therapeutic option cancer.

Язык: Английский

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Decomposable Nanoagonists Enable NIR‐Elicited cGAS‐STING Activation for Tandem‐Amplified Photodynamic‐Metalloimmunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(21)

Опубликована: Фев. 14, 2024

Activation of the cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway has emerged as an efficient strategy to improve therapeutic outcomes immunotherapy. However, "constantly active" mode current STING agonist delivery strategies typically leads off-target toxicity and hyperimmunity. To address this critical issue, herein a metal-organic frameworks-based nanoagonist (DZ@A7) featuring tumor-specific near-infrared (NIR) light-enhanced decomposition is constructed for precisely localized activation photodynamic-metalloimmunotherapy. The engineered enabled generation mitochondria-targeted reactive oxygen species under NIR irradiation specifically release mitochondrial DNA (mtDNA) inhibit repair nuclear via hypoxia-responsive drugs. Oxidized tumor mtDNA serves endogenous danger-associated molecular pattern that activates cGAS-STING pathway. Concurrently, NIR-accelerated zinc ions overloading in cancer cells further enhance cGAS enzymatic activity through metalloimmune effects. By combining synergistically enhanced triggered by irradiation, facilitated maturation dendritic infiltration cytotoxic T lymphocytes primary eradication, which also established long-term anti-tumor immunity suppress metastasis. Therefore, developed NIR-triggered, agonist-free, tandem-amplified pathway, thereby offering distinct paradigm

Язык: Английский

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Fusobacterium nucleatum in tumors: from tumorigenesis to tumor metastasis and tumor resistance

Cancer Biology & Therapy, Год журнала: 2024, Номер 25(1)

Опубликована: Янв. 30, 2024

Fusobacterium nucleatum, an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role cancer progression and prognosis. While extensive research revealed mechanistic links between nucleatum colorectal cancer, a comprehensive review spanning presence metastatic implications cancers beyond origin is conspicuously absent. This paper broadens our perspective from to various malignancies associated with including oral, pancreatic, esophageal, breast, gastric cancers. Our central focus unravel mechanisms governing colonization, initiation, promotion of metastasis across diverse types. Additionally, we explore nucleatum's adverse impacts on therapies, particularly within domains immunotherapy chemotherapy. Furthermore, this underscores clinical significance as potential tumor biomarker therapeutic target, offering novel outlook applicability detection prognostic assessment.

Язык: Английский

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AND Logic Gate-Regulated DNAzyme Nanoflower for Monitoring the Activity of Multiple DNA Repair Enzymes

Analytical Chemistry, Год журнала: 2024, Номер 96(5), С. 2117 - 2123

Опубликована: Янв. 25, 2024

Despite the progress that has been made in diverse DNA-based nanodevices to situ monitor activity of DNA repair enzymes living cells, significance improving both sensitivity and specificity remained largely neglected understudied. Herein, we propose a regulatable nanodevice specifically for early evaluation cancer mediated by genomic instability. Concretely, an AND logic gate-regulated DNAzyme nanoflower was rationally designed self-assembly duplex modified with apurinic/apyrimidinic (AP) site methyl lesion site. The could be reconfigured under AP sites O6-methylguanine endonuclease 1 (APE1) methyltransferase (MGMT) produce fluorescent signal, realizing sensitive monitoring APE1 MGMT. Compared free duplex, response increased 60%, due effective enrichment probes structure. More importantly, have demonstrated dual-enzyme activated strategy allows imaging specific cells gate manner using MCF-7 as cell model, imaging. This multifunctional provides simple tool simultaneously visualizing multiple enzymes, holding great potential clinical diagnosis drug discovery.

Язык: Английский

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