The current knowledge concerning solid cancer and therapy DOI
Masoud Najafi, Jamal Majidpoor, Heidar Toolee

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2021, Volume and Issue: 35(11)

Published: Aug. 31, 2021

Abstract Solid cancers comprise a large number of new cases and deaths from cancer each year globally. There are strategies for addressing tumors raised solid organs including surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, combinational stem cell extracellular vesicle (EV) therapy. Surgery, chemotherapy the dominant cures, but not always effective, in which even localized tumor there is possibility relapse after surgical resection. Over half patients will receive radiotherapy as part their therapeutic schedule. Radiotherapy can cause an abscopal response boosting activity immune system outside local field radiation, it may also unwanted bystander effect, predisposing nonradiated cells into carcinogenesis. In context checkpoint inhibition known standard‐of‐care, major concern regard with cold that show low responses to such Stem‐cell therapy be used send prodrugs toward area; this strategy, however, has its own predicaments, attraction other sites healthy tissues instability. A substitute quite novel strategy use EVs, by virtue stability potential cross biological barriers long‐term storage contents. Combination current focus. Despite advances field, still unmet concerns area effective raising challenges opportunities future investigations.

Language: Английский

Antibody drug conjugate: the “biological missile” for targeted cancer therapy DOI Creative Commons
Zhiwen Fu, Shijun Li, Sifei Han

et al.

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

Published: March 22, 2022

Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to cytotoxic drug via chemical linker. It combines both the advantages highly specific targeting ability and potent killing effect achieve accurate efficient elimination cancer cells, which has become one hotspots for research development anticancer drugs. Since first ADC, Mylotarg

Language: Английский

Citations

892
Targeting the tumor stroma for cancer therapy DOI Creative Commons
Maosen Xu, Tao Zhang,

Ruolan Xia

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Nov. 2, 2022

Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part the tumor microenvironment, stroma is highly dynamic, heterogeneous commonly tumor-type specific, it mainly includes noncellular compositions such as extracellular matrix unique cancer-associated vascular system well a wide variety cellular components including activated fibroblasts, mesenchymal cells, pericytes. All these elements operate with each other in coordinated fashion collectively promote initiation, progression, metastasis therapeutic resistance. Over past few decades, numerous studies have been conducted to study interaction crosstalk between neoplastic cells. Meanwhile, we also witnessed exponential increase investigation recognition critical roles solid tumors. A series clinical trials targeting launched continually. In this review, introduce discuss current advances understanding various their cancers. We elaborate on potential novel approaches for tumor-stroma-based targeting, aim leap from bench bedside.

Language: Английский

Citations

160
Cell-free DNA analysis in current cancer clinical trials: a review DOI Creative Commons
Mireya Cisneros-Villanueva, Lizbett Hidalgo Pérez, M. Rios-Romero

et al.

British Journal of Cancer, Journal Year: 2022, Volume and Issue: 126(3), P. 391 - 400

Published: Jan. 13, 2022

Abstract Cell-free DNA (cfDNA) analysis represents a promising method for the diagnosis, treatment selection and clinical follow-up of cancer patients. Although its general methodological feasibility usefulness has been demonstrated, several issues related to standardisation technical validation must be addressed routine application in cancer. In this regard, most cfDNA applications are still limited trials, proving value settings. paper, we review current trials involving cfDNA/ctDNA highlight those where it useful patient stratification, or development novel approaches early diagnosis. Our query included including terms ‘cfDNA’, ‘ctDNA’, ‘liquid biopsy’ AND ‘cancer OR neoplasm’ FDA EMA public databases. We identified 1370 (FDA = 1129, 241) liquid-biopsy These show results detection confirm as tool real-time monitoring acquired therapy resistance, accurate disease-progression surveillance improvement treatment, situations that result better quality life extended overall survival

Language: Английский

Citations

137
Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor–Resistant, EGFR-Mutated Non–Small Cell Lung Cancer DOI Creative Commons
Pasi A. Jänne,

Christina Baik,

Wu‐Chou Su

et al.

Cancer Discovery, Journal Year: 2021, Volume and Issue: 12(1), P. 74 - 89

Published: Sept. 21, 2021

Receptor tyrosine-protein kinase ERBB3 (HER3) is expressed in most EGFR-mutated lung cancers but not a known mechanism of resistance to EGFR inhibitors. HER3-DXd an antibody-drug conjugate consisting HER3 antibody attached topoisomerase I inhibitor payload via tetrapeptide-based cleavable linker. This phase I, dose escalation/expansion study included patients with locally advanced or metastatic non-small cell cancer (NSCLC) prior tyrosine (TKI) therapy. Among 57 receiving 5.6 mg/kg intravenously once every 3 weeks, the confirmed objective response rate by blinded independent central review (Response Evaluation Criteria Solid Tumors v1.1) was 39% [95% confidence interval (CI), 26.0-52.4], and median progression-free survival 8.2 (95% CI, 4.4-8.3) months. Responses were observed unknown TKI mechanisms. Clinical activity across broad range membrane expression. The common grade ≥3 treatment-emergent adverse events hematologic toxicities. has clinical TKI-resistant mechanisms, providing approach treat drug-resistant cancers. SIGNIFICANCE: In NSCLC, after disease progression on therapy, treatment approaches include genotype-directed therapy targeting chemotherapy. demonstrated spanning could present future option agnostic mechanism.See related commentary Lim et al., p. 16.This article highlighted Issue feature, 1.

Language: Английский

Citations

120
Acquired resistance to third-generation EGFR-TKIs and emerging next-generation EGFR inhibitors DOI Creative Commons
Xiaojing Du, Biwei Yang, Quanlin An

et al.

The Innovation, Journal Year: 2021, Volume and Issue: 2(2), P. 100103 - 100103

Published: April 3, 2021

The discovery that mutations in the EGFR gene are detected up to 50% of lung adenocarcinoma patients, along with development highly efficacious epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), has revolutionized treatment this frequently occurring malignancy. Indeed, clinical success these TKIs constitutes a critical milestone targeted cancer therapy. Three generations EGFR-TKIs currently approved for mutation-positive non-small cell (NSCLC). first-generation include erlotinib, gefitinib, lapatinib, and icotinib; second-generation ErbB family blockers afatinib, neratinib, dacomitinib; whereas osimertinib, by FDA on 2015, is third-generation TKI targeting harboring specific mutations. Compared first- TKIs, display significant advantage terms patient survival. For example, median overall survival NSCLC patients receiving osimertinib reached 38.6 months. Unfortunately, however, like other therapies, new mutations, as well additional drug-resistance mechanisms emerge rapidly after treatment, posing formidable obstacles therapeutics aimed at surmounting chemoresistance. In review, we summarize molecular underlying resistance ongoing efforts address overcome We also discuss current status fourth-generation inhibitors, which great value overcoming appear have greater therapeutic benefits clinic.

Language: Английский

Citations

114
Emerging strategies to overcome resistance to third-generation EGFR inhibitors DOI Creative Commons

Kunyu Shi,

Guan Wang, Junping Pei

et al.

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

Published: July 15, 2022

Abstract Epidermal growth factor receptor (EGFR), the for members of epidermal family, regulates cell proliferation and signal transduction; moreover, EGFR is related to inhibition tumor proliferation, angiogenesis, invasion, metastasis, apoptosis. Therefore, has become an important target treatment cancer, including non-small lung head neck breast glioma, cervical bladder cancer. First- third-generation inhibitors have shown considerable efficacy significantly improved disease prognosis. However, most patients develop drug resistance after treatment. The challenge overcoming intrinsic acquired in primary recurrent cancer mediated by mutations thus driving search alternative strategies design new therapeutic agents. In view inhibitors, understanding intricate mechanisms will offer insight development more advanced targeted therapies. this review, we discuss molecular review recent resistance, challenges, future directions.

Language: Английский

Citations

102
Treatment strategies and outcomes for patients with EGFR-mutant non-small cell lung cancer resistant to EGFR tyrosine kinase inhibitors: Focus on novel therapies DOI Creative Commons
Melissa L. Johnson,

Marina Chiara Garassino,

Tony Mok

et al.

Lung Cancer, Journal Year: 2022, Volume and Issue: 170, P. 41 - 51

Published: May 21, 2022

Abstract

Tyrosine kinase inhibitors (TKIs) are the standard of care for patients with non-small cell lung cancer (NSCLC) that harbor mutations epidermal growth factor receptor (EGFR) gene. First-line therapy these is often osimertinib, a third-generation EGFR TKI. Erlotinib, gefitinib, afatinib, and dacomitinib first- second-generation TKIs also available. However, almost all eventually develop disease progression due to TKI-acquired resistance. The mechanisms resistance after TKI exposure involve or its downstream pathways. While frequently utilized strategy combating acquired remains platinum-based chemotherapy, clinical investigation promising novel agents targeting common such as MET, HER2, HER3 increased interest. In this review, we discuss in EGFR-mutant NSCLC, examine current treatment standards, developing therapies. Both EGFR-dependent (involving secondary EGFR) EGFR-independent (mutations bypass signaling histologic transformation) considered. Several strategies emerging overcome mechanisms, understanding identification specific EGFR-TKI continues improve. treatments development aim target resistance, including MET-, HER2-, HER3-directed molecular profiling at time initial may help identify relevant Clinical trial participation vital continued NSCLC.

Language: Английский

Citations

84
Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers DOI Creative Commons
Jinfeng Yu, Fang Tong,

Chengyu Yun

et al.

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Feb. 28, 2022

Members of the human epidermal growth factor receptor (HER) family, which includes HER1 (also known as EGFR), HER2, HER3 and HER4, have played a central role in regulating cell proliferation, survival, differentiation migration. The overexpression HER family has been recognized one most common cellular dysregulation associated with wide variety tumor types. Antibody-drug conjugates (ADCs) represent new promising class anticancer therapeutics that combine cancer specificity antibodies cytotoxicity chemotherapeutic drugs. Two HER2-directed ADCs, trastuzumane-emtansine (T-DM1) trastuzumab-deruxtecan (DS-8201a), approved for HER2-positive metastatic breast by U.S. Food Drug Administration (FDA) 2013 2019, respectively. A third ADC, disitamab vedotin (RC48), locally advanced or gastric gastroesophageal junction NMPA (National Medical Products Administration) China 2021. total 11 ADCs target receptors (EGFR, HER2 HER3) are currently under clinical trials. In this review article, we summarize three (T-DM1, DS-8201a RC48), together investigational EGFR-directed (ABT-414, MRG003 M1231), (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 SBT6050) HER3-directed ADC (U3-1402). Lastly, discuss major challenges development highlight possible future directions to tackle these challenges.

Language: Английский

Citations

80
Aberrant m5C hypermethylation mediates intrinsic resistance to gefitinib through NSUN2/YBX1/QSOX1 axis in EGFR-mutant non-small-cell lung cancer DOI Creative Commons
Yueqin Wang, Jingyao Wei, Luyao Feng

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: May 9, 2023

RNA 5-methylcytosine (m5C) modification plays critical roles in the pathogenesis of various tumors. However, function and molecular mechanism m5C tumor drug resistance remain unclear.The correlation between methylation, writer NOP2/Sun methyltransferase family member 2 (NSUN2) EGFR-TKIs was determined non-small-cell lung cancer (NSCLC) cell lines patient samples. The effects NSUN2 on were investigated by gain- loss-of-function assays vitro vivo. RNA-sequencing (RNA-seq), bisulfite sequencing (RNA-BisSeq) methylated immunoprecipitation-qPCR (MeRIP-qPCR) performed to identify target gene involved resistance. Furthermore, regulatory modulating expression functional rescue puromycin incorporation assays.RNA hypermethylation significantly correlated with intrinsic EGFR-TKIs. Overexpression resulted gefitinib recurrence, while genetic inhibition led regression overcame Integrated RNA-seq m5C-BisSeq analyses identified quiescin sulfhydryl oxidase 1 (QSOX1) as a potential aberrant modification. QSOX1 coding sequence region, leading enhanced translation through reader Y-box binding protein (YBX1).Our study reveals via NSUN2-YBX1-QSOX1 axis mediating EGFR-mutant NSCLC.

Language: Английский

Citations

80
Current Landscape of Therapeutic Resistance in Lung Cancer and Promising Strategies to Overcome Resistance DOI Open Access
Adnin Ashrafi, Zakia Akter, Pouya Modareszadeh

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(19), P. 4562 - 4562

Published: Sept. 20, 2022

Lung cancer is one of the leading causes cancer-related deaths worldwide with a 5-year survival rate less than 18%. Current treatment modalities include surgery, chemotherapy, radiation therapy, targeted and immunotherapy. Despite advances in therapeutic options, resistance to therapy remains major obstacle effectiveness long-term treatment, eventually insensitivity, poor progression-free survival, disease relapse. Resistance mechanisms stem from genetic mutations and/or epigenetic changes, unregulated drug efflux, tumor hypoxia, alterations microenvironment, several other cellular molecular alterations. A better understanding these crucial for targeting factors involved resistance, establishing novel antitumor targets, developing strategies resensitize cells towards treatment. In this review, we summarize diverse driving radiotherapy, immunotherapy, promising help overcome resistance.

Language: Английский

Citations

70