The changing treatment landscape of EGFR-mutant non-small-cell lung cancer

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

Language: Английский

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Dormant Tumor Cells: Current Opportunities and Challenges in Clinical Practice

Onco, Journal Year: 2025, Volume and Issue: 5(1), P. 3 - 3

Published: Jan. 10, 2025

Tumor dormancy plays a pivotal role in cancer relapse. Dormant tumor cells have been identified distant sites, even early-stage tumors, and are associated with worse outcomes. This review explores the current understanding of molecular cellular mechanisms behind dormancy, including immune system microenvironment. Targeting dormant could be therapeutic strategy to offer long-term remission potentially cure cancer. Unfortunately, translation this knowledge clinical practice is lacking. We assess feasibility detecting measuring practice, give an overview potential targets, both terms maintaining state, eradicating population.

Language: Английский

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Targeting ferroptosis: a promising approach for treating lung carcinoma

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 29, 2025

Abstract Lung carcinoma incidence and fatality rates remain among the highest on a global scale. The efficacy of targeted therapies immunotherapies is commonly compromised by emergence drug resistance other factors, resulting in lack durable therapeutic benefits. Ferroptosis, distinct pattern cell death marked buildup iron-dependent lipid peroxides, has been shown to be novel potentially more effective treatment for lung carcinoma. However, mechanism regulatory network ferroptosis are exceptionally complex, many unanswered questions remain. In addition, research diagnosis cancer growing exponentially. Therefore, it necessary provide thorough summary latest advancements field ferroptosis. Here, we comprehensively analyze mechanisms underlying preconditions ferroptosis, defense system, associated molecular networks. potential strategies also highlighted. Targeting improves tumor enhances effectiveness drugs immunotherapies. These findings may shed fresh light management carcinoma, as well development related

Language: Английский

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Anastasis and Other Apoptosis-Related Prosurvival Pathways Call for a Paradigm Shift in Oncology: Significance of Deintensification in Treating Solid Tumors

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1881 - 1881

Published: Feb. 22, 2025

What is apoptosis? The Nomenclature Committee on Cell Death and numerous other pioneering cancer/p53 biologists use the terms "apoptosis" "cell death" interchangeably, disregard mind-numbing complexity heterogeneity that exists within a tumor (intratumor heterogeneity), contribution of polyploid giant cancer cells (PGCCs; root causes therapy resistance relapse) to this heterogeneity, then propose novel apoptosis-stimulating anticancer strategies. This shocking for following three reasons. First, clinical studies reported since 1990s have revealed increased apoptosis in solid tumors associated with diversity poor prognosis. Second, we known years dying (apoptotic) release panel secretions (e.g., via phoenix rising pathways) promote metastatic outgrowth. Third, over decade ago, it was demonstrated can recover from late stages (after formation apoptotic bodies) homeostatic process anastasis, resulting emergence aggressive variants. cell surface expression CD24 has recently been be preferentially enriched recovered (anastatic) exhibit tumorigenic properties. These related discoveries outlined herein call paradigm shift oncology focus strategies minimize occurrence treacherous tumor-repopulating events therapy-induced dormancy reactivation). They also raise an intriguing question: deregulated anastasis (rather than evasion apoptosis) hallmark cancer?

Language: Английский

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Adaptation of redox metabolism in drug-tolerant persister cells is a vulnerability to prevent relapse in pancreatic cancer

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Pancreatic Ductal Adenocarcinoma (PDAC) remains a major unresolved disease because of its remarkable therapeutic resistance. Even patients who respond to initial therapy experience relapse in most cases. The mechanisms underlying therapy-acquired resistance supporting are poorly understood. In this study, we aimed determine the metabolic features PDAC during relapse, specifically adaptations mitochondrial oxidative metabolism. We used preclinical mouse models (patient-derived xenografts and murine syngeneic allografts) that present regression under chemotherapeutic treatment but after certain time. Relapsed tumors were analyzed ex vivo by flow cytometry measure redox characteristics. Molecular investigated quantification ATP antioxidants levels, RT-qPCR bulk RNA-sequencing. We show increased mass, superoxide anions, total ROS relapsed compared control both models; membrane potential is model only. These also observed treatment-induced at onset. At molecular level, antioxidant defenses treatment. data suggest occurring may favor survival drug-tolerant persister (DTP) cells, which persist subsequent minimal residual responsible for cancer relapse. Finally, combined arsenic trioxide (ROS inducer) buthionine sulfoximine (glutathione synthesis inhibitor) able completely prevent xenografts. conclusion, metabolism vulnerability pancreatic DTP cells can be targeted

Language: Английский

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Research progress in MCM family: Focus on the tumor treatment resistance

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116408 - 116408

Published: March 12, 2024

Malignant tumors constitute a significant category of diseases posing severe threat to human survival and health, thereby representing one the most challenging pressing issues in field biomedical research. Due their malignant nature, which is characterized by high potential for metastasis, rapid dissemination, frequent recurrence, prevailing approach clinical oncology involves comprehensive treatment strategy that combines surgery with radiotherapy, chemotherapy, targeted drug therapies, other interventions. Treatment resistance remains major obstacle management tumors, serving as primary cause failure integrated tumor therapies critical factor contributing patient relapse mortality. The Minichromosome Maintenance (MCM) protein family comprises functional proteins closely associated development therapy.The influence MCMs manifests through various pathways, encompassing modulation DNA replication, cell cycle regulation, damage repair mechanisms. Consequently, this leads an enhanced tolerance cells drugs, radiation. review explores specific roles MCM cancer strategies. Its objective enhance our comprehension mechanisms therapy, presenting novel targets research aimed at overcoming treatment. This bears substantial relevance.

Language: Английский

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Farnesyltransferase inhibition overcomes oncogene-addicted non-small cell lung cancer adaptive resistance to targeted therapies

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 27, 2024

Abstract Drug-tolerance has emerged as one of the major non-genetic adaptive processes driving resistance to targeted therapy (TT) in non-small cell lung cancer (NSCLC). However, kinetics and sequence molecular events governing this response remain poorly understood. Here, we combine real-time monitoring cell-cycle dynamics single-cell RNA sequencing a broad panel oncogenic addiction such EGFR-, ALK-, BRAF- KRAS-mutant NSCLC, treated with their corresponding TT. We identify common path drug adaptation, which invariably involves alveolar type 1 (AT1) differentiation Rho-associated protein kinase (ROCK)-mediated cytoskeletal remodeling. also isolate characterize rare population early escapers, represent earliest resistance-initiating cells that emerge first hours treatment from AT1-like population. A phenotypic screen farnesyltransferase inhibitors (FTI) tipifarnib most effective drugs preventing relapse TT vitro vivo several models addiction, is confirmed by genetic depletion farnesyltransferase. These findings pave way for development treatments combining FTI effectively prevent tumor oncogene-addicted NSCLC patients.

Language: Английский

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Early tolerance and late persistence as alternative drug responses in cancer

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 3, 2025

Bacteria withstand antibiotic treatment through three alternative mechanisms: resistance, persistence or tolerance. While resistance and have been described, whether drug-induced tolerance exists in cancer cells remains largely unknown. Here, we show that human elicit a tolerant response when exposed to commonly used chemotherapy regimens, propelled by the pervasive activation of autophagy, leading comprehensive DNA damage repair pathways. After prolonged drug exposure, such responses morph into persistence, whereby increased is entirely reversed. The central regulator mitophagy PINK1 drives this reduction via cytoplasmic relocalization cell identity master HNF4A, thus hampering HNF4A transcriptional genes. We conclude exposing relevant standard-of-care antitumour therapies induces might be broadly exploited increase impact first-line, adjuvant treatments debulking advanced cancers. are able mechanisms, authors investigate mechanisms as defined bacteria also apply cells, finding exposure elicits an atavistic providing key survival advantages.

Language: Английский

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An aggregation-induced emission-active lysosome hijacker: sabotaging lysosomes to boost photodynamic therapy efficacy and conquer tumor therapeutic resistance

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101564 - 101564

Published: Feb. 8, 2025

Therapeutic resistance is a major challenge in clinical cancer theranostics, often leading to treatment failure and increased patient mortality. Breaking this therapeutic deadlock, enhancing the efficacy of treatments, ultimately improving survival rates are both highly desirable significantly challenging goals. Herein, we have developed new fluorescent luminogen, QM-DMAC, which features aggregation-induced emission (AIE), exceptional viscosity-responsive properties. The AIE-active QM-DMAC can specifically stain lysosomes tumor cells, offering high signal-to-noise ratio enabling specific visualization variations lysosomal viscosity, such as those induced by inflammation or autophagy. Furthermore, effectively generates reactive oxygen species (ROS) under white light irradiation, precisely induces ROS-mediated membrane permeabilization (LMP) lysosome rupture. This causes severe cell damage restores sensitivity cells radiotherapy chemotherapy. Thus, serves efficient lysosome-targeting photosensitizer an excellent sensitizer. innovative "lysosome hijacking" strategy maximizes photodynamic therapy, conquering boosting synergistic effect when integrated with conventional It provides novel approach design theranostic agents for theranostics.

Language: Английский

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Therapy resistance: modulating evolutionarily conserved heat shock protein machinery in cancer

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217571 - 217571

Published: Feb. 1, 2025

Language: Английский

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