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Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/ Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study

ÈðÔóÌæÄᣨBPI-7711£©ÖÎÁƾֲ¿ÍíÆÚ»òתÒÆÐÔ/¸´·¢ÐÔ EGFR T790M Í»±äÐÍ·ÇСϸ°û·Î°©»¼ÕßµÄÁÆЧÓ밲ȫÐÔ£ºÒ»Ïî2bÆÚÑо¿

Issue JOURNAL OF THORACIC ONCOLOGY 2022, Volume 17 Issue 11 1306-1317

ÆÚ¿¯£º¡¶Ðز¿Ö×ÁöÔÓÖ¾¡·£¨JOURNAL OF THORACIC ONCOLOGY£©£¬2022Ä꣬µÚ17¾íµÚ11ÆÚ£¬1306-1317Ò³

Author Shi Yuankai / Wu Shiman / Wang Ke / Cang Shundong / Yao Wenxiu / Fan Yun / Wu Lin / Huang Meijuan / Li Xingya / Pan Yueyin / Yang Zhixiong / Zhu Bo / Chen Gongyan / Shi Jianhua / Sun Meili / Fang Jian / Wang Lijun / Chen Zhaohong / Liu Chunling / Li Jingzhang / Liu Jiwei / Sun Shenghua / Zhao Yanqiu / Guo Yanzhen / Meng Zili / Liu Zhefeng / Han Zhigang / Lu Hong / Ma Rui / Hu Sheng / Zhao Guofang / Liu Zheng / Xie Congying / Zhong Diansheng / Zhao Hui / Yu Huiqing / Zhang Longzhen / Bi Minghong / Yi Shanyong / Guo Shuliang / Yi Tienan / Li Wen / Lin Yingcheng / Shu Yongqian / Chen Zhendong / Guo Zhongliang / Greco Michael / Wang Tingting / Shen Haijiao

Keywords Rezivertinib / BPI-7711 / NSCLC / EGFR T790M mutation / Third-generation EGFR TKI

Abstract

Introduction: Rezivertinib (BPI-7711) is a novel third -generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M muta-tion. This study aimed to evaluate the efficacy and safety of rezivertinib in patients with locally advanced or metastatic/ recurrent EGFR T790M-mutated NSCLC. Methods: Patients with locally advanced or metastatic/ recurrent NSCLC with confirmed EGFR T790M mutation who progressed after first-/second-generation EGFR TKI therapy or primary EGFR T790M mutation were enrolled. Patients received rezivertinib at 180 mg orally once daily until disease progression, unacceptable toxicity, or with-drawal of consent. The primary end point was objective response rate (ORR) assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival, and safety. This study is registered with Clinical Trials.gov (NCT03812809). Results: A total of 226 patients were enrolled from July 5, 2019, to January 22, 2020. By the data cutoff date on January 24, 2022, the median duration of follow-up was 23.3 months (95% confidence interval [CI]: 22.8-24.0). The ORR by blinded independent central review was 64.6% (95% CI: 58.0%-70.8%), and DCR was 89.8% (95% CI: 85.1%-93.4%). The median duration of response was 12.5 months (95% CI: 10.0-13.9), and median PFS was 12.2 months (95% CI: 9.6-13.9). The median overall survival was 23.9 months (95% CI: 20.0-not calculated [NC]). Among 91 (40.3%) patients with central nervous system (CNS) metastases, the median CNS PFS was 16.6 months (95% CI: 11.1-NC). In 29 patients with more than or equalto one brain target lesion at baseline, the CNS ORR and CNS DCR were 69.0% (95% CI: 49.2%-84.7%) and 100% (95% CI: 88.1%-100%), respectively. Time to progression of CNS was 16.5 months (95% CI: 9.7-NC). Of 226 patients, 188 (83.2%) had at least one treatment-related adverse event, whereas grade more than or equal to 3 occurred in 45 (19.9%) patients. No interstitial lung disease was reported.Conclusions: Rezivertinib was found to have promising efficacy and favorable safety profile for patients with locally advanced or metastatic/recurrent NSCLC with EGFR T790M mutation.(c) 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Cite this article as: [1]Shi Yuankai, Wu Shiman, Wang Ke, et al.Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/ Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study[J].JOURNAL OF THORACIC ONCOLOGY,2022,17(11):1306-1317.

HIF1¦Á-SP1 interaction disrupts the circ-0001875/miR-31-5p/SP1 regulatory loop under a hypoxic microenvironment and promotes non-small cell lung cancer progression

ȱÑõ΢»·¾³ÏÂHIF1¦ÁÓëSP1Ï໥×÷ÓÃÆÆ»µcirc-0001875/miR-31-5p/SP1µ÷¿Ø»·Â·²¢´Ù½ø·ÇСϸ°û·Î°©½øÕ¹

Issue JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 2022, Volume 41 Issue 1

ÆÚ¿¯£º¡¶ÊµÑéÓëÁÙ´²°©Ö¢Ñо¿ÔÓÖ¾¡·£¨JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH£©£¬2022Ä꣬µÚ41¾íµÚ1ÆÚ

Author Wu Dong / Chen Tingting / Zhao Xuanna / Huang Dan / Huang Jiawei / Huang Yujie / Huang Qiu / Liang Zhu / Chen Chunyuan / Chen Min / Li Dongming / Wu Bin / Li Lixia

Keywords Non-small cell lung cancer / Has-circ-0001875 / miR-31-5p / SP1 / EMT / Hypoxia / Regulatory loop

Abstract

Background Circular RNAs (circRNAs) play an important role in the progression of non-small cell lung cancer (NSCLC), especially under tumor hypoxia. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC are largely unknown. Methods High-throughput RNA sequencing was performed to identify significantly expressed circRNAs in NSCLC tissues. The functions of circ-0001875 in NSCLC cells were investigated in vitro and in vivo. The regulatory relationships of circ-0001875, miR-31-5p and SP1 were examined by dual luciferase reporter assays and rescue experiments. The signal pathway of epithelial-to-mesenchymal transition and the formation of filopodia were analyzed by western blot and immunofluorescence staining. The binding of SP1 to Alu elements was evaluated by RNA immunoprecipitation, and the HIF1 alpha and SP1 interaction was detected by co-immunoprecipitation. Results We identified the novel Has_circ_0001875 as a significantly upregulated circRNA in NSCLC tissues and cell lines. circ-0001875 promoted the proliferation and metastasis of NSCLC both in vitro and in vivo, and induced NSCLC cells to extend filopodia. Mechanistically, circ-0001875 sponged miR-31-5p to regulate SP1, influencing epithelial-to-mesenchymal transition via the TGF beta/Smad2 signal pathway. SP1 negatively regulated circ-0001875 formation through an AluSq-dependent feedback loop, which was disrupted by competitive binding of HIF1 alpha to SP1 under hypoxia condition. The circ-0001875/miR-31-5p/SP1 axis was associated with the clinical features and prognosis of NSCLC patients. Conclusions Our results revealed that the circ-0001875/miR-31-5p/SP1 axis and the complex regulatory loops influence NSCLC progression. These findings provide new insights into the regulation of circRNA formation under tumor hypoxia.

Cite this article as: [1]Wu Dong, Chen Tingting, Zhao Xuanna, et al.HIF1¦Á-SP1 interaction disrupts the circ-0001875/miR-31-5p/SP1 regulatory loop under a hypoxic microenvironment and promotes non-small cell lung cancer progression[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2022,41(1).

Targeting MEX3A attenuates metastasis of breast cancer via ¦Â-catenin signaling pathway inhibition

°ÐÏò MEX3A ͨ¹ýÒÖÖÆ ¦Â- Á¬»·µ°°×ÐźÅͨ·¼õÈõÈéÏÙ°©×ªÒÆ

Issue CANCER LETTERS 2021, Volume 521 50-63

ÆÚ¿¯£º¡¶°©Ö¢¿ì±¨¡·£¨CANCER LETTERS£©£¬2021Ä꣬µÚ 521¾í£¬50-63Ò³

Author Wang Yun / Liang Qian / Lei Kefeng / Zhu Qingqing / Zeng Delong / Liu Yuhong / Lu Yingsi / Kang Tingting / Tang Nannan / Huang Lifen / Ye Liping / Tang Di / Zhu Chengming

Keywords MEX3A / Breast cancer / Wnt/beta / DKK1 / Metastasis

Abstract

Metastasis is the major cause of mortality in patients with breast cancer. Understanding the metastatic mechanism to guide clinical diagnoses and the treatment of breast cancer remains a challenge. We found that the expression of Mex-3 RNA binding family member A (MEX3A) was upregulated significantly and related to tumor grade in breast cancer. The results of in vitro and in vivo studies showed that knockdown of MEX3A inhibited the metastasis and impaired the stemness of breast cancer cells. Furthermore, activation of the beta-catenin signaling pathway was discovered as a molecular intermediate of MEX3A-mediated regulation. We also found that ectopic expression of beta-catenin restored the migration ability, invasion ability, and CD44(+)/CD24(-) percentage of MDAMB-231 and BT549 cells when MEX3A was depleted. In addition, we revealed that MEX3A positively regulated the expression of beta-catenin by downregulating Dickkopf WNT signaling pathway inhibitor 1 (DKK1) expression. Therefore, a previously undiscovered role of MEX3A comprising a critical contribution to promoting metastasis and maintaining the stemness of breast cancer via the Wnt/beta-catenin pathway was demonstrated in the present study.

Cite this article as: [1]Wang Yun, Liang Qian, Lei Kefeng, et al.Targeting MEX3A attenuates metastasis of breast cancer via ¦Â-catenin signaling pathway inhibition[J].CANCER LETTERS,2021,521:50-63.

Survival differences between HER2-0 and HER2-low-expressing breast cancer- A meta-analysis of early breast cancer patients

HER2 ÒõÐÔÓëHER2µÍ±í´ïÈéÏÙ°©»¼ÕßµÄÉú´æ²îÒì ¡ª¡ª Ò»ÏîÔçÆÚÈéÏÙ°©»¼ÕßµÄÜöÝÍ·ÖÎö

Issue CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY 2023, Volume 185

ÆÚ¿¯£º¡¶Ö×ÁöѧÓëѪҺѧÆÀÂÛ¡·£¨CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY£©£¬2023Ä꣬µÚ185¾í

Author Yang Ciqiu / Zhang Xiaoqi / Chen Yitian / Li Peiyong / Zhang Junsheng / Xu Aiqi / Huang Na / Liang Minting / Chen Yilin / Wang Kun

Keywords HER2-low-expressing breast cancer / HER2-zero breast cancer / Survival

Abstract

Background: HER2-low (human epidermal growth factor receptor 2) breast cancer takes up 40-50% in all breast cancer subtypes. The survival difference between HER2-low and HER2-zero breast cancers remain uncertain. Therefore, the aim of this study was to compare survival outcome of the two subtypes and to explore the impact of hormone receptor status. Methods: A comprehensive medical literature search was performed by searching PubMed, EMBASE, and the Cochrane Libraries up to August 2022. We included observational studies reporting hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). The results of individual studies were pooled by random-effects models using Stata 16.0. Seventeen articles with a total of 78984 breast cancer patients were included in the meta-analysis. Results: We observed a statistically significant association between low HER2 expression and better breast cancer survival outcomes (OS: HR: 0.83; 95% confidence interval: 0.75, 0.90; DFS/RFS: HR: 0.83; 95% confidence interval: 0.75, 0.91). In a subgroup analysis, we found that HER2-low patients had better survival outcomes relative to hormone receptor-positive breast cancer patients (OS: HR: 0.87; 95% confidence interval: 0.81, 0.93; DFS/RFS: HR: 0.91; 95% confidence interval: 0.85, 0.96). Similarly, in triple-negative breast cancer patients, we also observed a positive association between HER2 low expression and better survival (OS: HR: 0.85; 95% confidence interval: 0.71, 0.98; DFS/RFS: HR: 0.85; 95% confidence interval: 0.74, 0.95). Conclusions: Our study showed that HER2-low breast cancer had better survival outcomes compared to HER2 negative breast cancer in patients with early stage breast cancer, regardless of hormone receptor status. Registration: This meta-analysis was registered with PROSPERO (CRD42022335704) on June 10, 2022. Availability of data and materials: All data generated or analysed during this study are included in this published article [and its supplementary information files].

Cite this article as: [1]Yang Ciqiu, Zhang Xiaoqi, Chen Yitian, et al.Survival differences between HER2-0 and HER2-low-expressing breast cancer- A meta-analysis of early breast cancer patients[J].CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY,2023,185.

Efficacy and potential resistance mechanisms of afatinib in advanced non-small cell lung cancer patients with EGFR G719X/L861Q/S768I

°¢·¨ÌæÄáÖÎÁÆЯ´øEGFR G719X/L861Q/S768IÍ»±äµÄÍíÆÚ·ÇСϸ°û·Î°©»¼ÕßµÄÁÆЧ¼°Ç±ÔÚÄÍÒ©»úÖÆ

Issue CANCER 2022, Volume 128 Issue 21 3804-3814

ÆÚ¿¯£º¡¶°©Ö¢¡·£¨CANCER£©£¬2022Ä꣬µÚ128¾íµÚ21ÆÚ£¬3804-3814Ò³

Author Pang Lan-Lan / Gan Jia-Di / Tan Jia-Rong / Huang Yi-Hua / Liao Jun / Liang Wei-Ting / Deng Peng-Bo / Fang Wen-Feng

Keywords afatinib / G719X / L861Q / S768I / NSCLC / resistance / uncommon mutation

Abstract

Background Afatinib is the only currently approved EGFR-tyrosine kinase inhibitors for advanced non-small cell lung cancer (NSCLC) patients with EGFR G719X/L861Q/S768I. However, there are limited real-world data concerning the benefits and resistance mechanisms of afatinib in patients with these nonclassical mutations. To fill this gap, the present study was conducted. Methods All NSCLC patients treated with afatinib were screened, and patients with EGFR G719X/L861Q/S768I were enrolled into the analysis. Either tumor tissue or blood specimens were detected by the commercial next-generation sequencing (NGS) panels or amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) to figure out the mutation genotype. Results A total of 106 advanced NSCLC patients with EGFR G719X/L861Q/S768I received afatinib treatment. The benefits of afatinib exhibited heterogeneity in different mutation genotypes. Notably, at baseline, NGS testing was performed in 59 patients, and TP53 was the most frequently coexisting mutation. Patients with TP53 mutations obtained fewer survival benefits than those with TP53 wild-type. A total of 68 patients ultimately experienced progression, and 27 patients received NGS testing to clarify the potential resistance mechanisms. EGFR-T790M, CDK4 amplification, FGFR1 amplification, PIK3CA, MET amplification, RET fusions, HER2, and BRAF mutations were identified in three (11.1%), three (11.1%), three (11.1%), three (11.1%), three (11.1%), one (3.7%), one (3.7%), and one (3.7%) of the cases, respectively. Five patients underwent ARMS-PCR testing for detecting EGFR-T790M mutation, and only one patient was T790M-positive. Conclusions The present study elucidated the differential benefits of afatinib within different mutation genotypes and first revealed the spectrum of potential resistance mechanisms in patients with EGFR G719X/L861Q/S768I. The results of this study may provide practical clinical information that can guide optimal treatment in this setting.

Cite this article as: [1]Pang Lan-Lan, Gan Jia-Di, Tan Jia-Rong, et al.Efficacy and potential resistance mechanisms of afatinib in advanced non-small cell lung cancer patients with EGFR G719X/L861Q/S768I[J].CANCER,2022,128(21):3804-3814.

A Phase III, randomized, double-blind, placebo-controlled, multicenter study of fruquintinib in Chinese patients with advanced nonsquamous non-small-cell lung cancer - The FALUCA study

ß»à­ÌæÄáÖÎÁÆÖйúÍíÆÚ·ÇÁÛ·ÇСϸ°û·Î°©»¼ÕßµÄIIIÆÚËæ»ú˫䰲ο¼Á¶ÔÕÕ¶àÖÐÐÄÑо¿ ¡ª¡ªFALUCA Ñо¿

Issue LUNG CANCER 2020, Volume 146 252-262

ÆÚ¿¯£º¡¶·Î°©¡·£¨LUNG CANCER£©£¬2020Ä꣬µÚ146¾í£¬252-262Ò³

Author Lu Shun / Chen Gongyan / Sun Yuping / Sun Sanyuan / Chang Jianhua / Yao Yu / Chen Zhendong / Ye Feng / Lu Junguo / Shi Jianhua / He Jianxing / Liu Xiaoqing / Zhang Yiping / Liu Zhihua / Fang Jian / Cheng Ying / Hu Chunhong / Mao Weidong / Hu Yanping / Gong Youling / Shan Li / Yang Zhixiong / Song Yong / Li Wei / Bai Chong / Wang Buhai / Ma Rui / Zheng Zhendong / Liu Mingfang / Jie Zhijun / Cao Lejie / Liao Wangjun / Pan Hongming / Huang Dongning / Chen Yuan / Yang Jinji / Qin Shukui / Ma Shenglin / Liang Li / Liu Zhe / Zhou Jianying / Tao Min / Huang Yijiang / Qiu Feng / Huang Yunchao / Guan Sha / Peng Mengye / Su Weiguo

Keywords Non-small-cell lung cancer / Fruquintinib / VEGFR-TKI

Abstract

Objectives: Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population. Materials and methods: From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS). Results: Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P < 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P < 0.001). Hypertension was the most frequent treatment-emergent adverse event (>= grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires. Conclusion: Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.

Cite this article as: [1]Lu Shun, Chen Gongyan, Sun Yuping, et al.A Phase III, randomized, double-blind, placebo-controlled, multicenter study of fruquintinib in Chinese patients with advanced nonsquamous non-small-cell lung cancer - The FALUCA study[J].LUNG CANCER,2020,146():252-262.

A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma

ÓÃÓÚÔ¤²â³ÉÈË T ϸ°ûÁÜ°Íĸϸ°ûÁÜ°ÍÁö¸´·¢µÄCpG¼×»ù»¯·ÖÀàÆ÷

Issue CLINICAL CANCER RESEARCH 2020, Volume 26 Issue 14 3760-3770

ÆÚ¿¯£º¡¶ÁÙ´²°©Ö¢Ñо¿¡·£¨CLINICAL CANCER RESEARCH£©£¬2020Ä꣬µÚ26¾í£¬µÚ14ÆÚ£¬3760-3770Ò³

Author Tian Xiao-Peng / Su Ning / Wang Liang / Huang Wei-Juan / Liu Yan-Hui / Zhang Xi / Huang Hui-Qiang / Lin Tong-Yu / Ma Shu-Yun / Rao Hui-Lan / Li Mei / Liu Fang / Zhang Fen / Zhong Li-Ye / Liang Li / Lan Xiao-Liang / Li Juan / Liao Bing / Li Zhi-Hua / Tang Qiong-Lan / Liang Qiong / Shao Chun-Kui / Zhai Qiong-Li / Cheng Run-Fen / Sun Qi / Ru Kun / Gu Xia / Lin Xi-Na / Yi Kun / Shuang Yue-Rong / Chen Xiao-Dong / Dong Wei / Sun Cai / Sang Wei / Liu Hui / Zhu Zhi-Gang / Rao Jun / Guo Qiao-Nan / Zhou Ying / Meng Xiang-Ling / Zhu Yong / Hu Chang-Lu / Jiang Yi-Rong / Zhang Ying / Gao Hong-Yi / He Wen-Jun / Xia Zhong-Jun / Pan Xue-Yi / Hai Lan / Li Guo-Wei / Song Li-Yan / Kang Tie-Bang / Xie Dan / Cai Qing-Qing

Abstract

Purpose: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. Experimental Design: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). Results: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. Conclusions: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

Cite this article as: [1]Tian Xiao-Peng, Su Ning, Wang Liang, et al.A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma[J].CLINICAL CANCER RESEARCH,2020,26(14):3760-3770.

The crosstalk between oncogenic signaling and ferroptosis in cancer

°©Ö¢ÖÐÖ°©ÐźÅÓëÌúËÀÍöµÄÏ໥×÷ÓÃ

Issue CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY 2024, Volume 197

ÆÚ¿¯£º¡¶Ö×ÁöѧÓëѪҺѧÆÀÂÛ¡·£¨CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY£©£¬2024Ä꣬µÚ197¾í

Author Pang Qianghu / Tang Zhirou / Luo Lianxiang

Keywords ferroptosis / redox homeostasis / oxidative stress / oncogenic signaling / tumor

Abstract

Ferroptosis, a novel form of cell death regulation, was identified in 2012. It is characterized by unique features that differentiate it from other types of cell death, including necrosis, apoptosis, autophagy, and pyroptosis. Ferroptosis is defined by an abundance of iron ions and lipid peroxidation, resulting in alterations in subcellular structures, an elevation in reactive oxygen species (ROS), a reduction in glutathione (GSH) levels, and an augmentation in Fe (II) cytokines. Ferroptosis, a regulated process, is controlled by an intricate network of signaling pathways, where multiple stimuli can either enhance or hinder the process. This review primarily examines the defensive mechanisms of ferroptosis and its interaction with the tumor microenvironment. The analysis focuses on the pathways that involve AMPK, p53, NF2, mTOR, System Xc-, Wnt, Hippo, Nrf2, and cGASSTING. The text discusses the possibilities of employing a combination therapy that targets several pathways for the treatment of cancer. It emphasizes the necessity for additional study in this field.

Cite this article as: [1]Pang Qianghu, Tang Zhirou, Luo Lianxiang.The crosstalk between oncogenic signaling and ferroptosis in cancer[J].CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY,2024,197.

Targeting of focal adhesion kinase enhances the immunogenic cell death of PEGylated liposome doxorubicin to optimize therapeutic responses of immune checkpoint blockade

°ÐÏòð¤×Å°ß¼¤Ã¸¿ÉÔöÇ¿¾ÛÒÒ¶þ´¼»¯Ö¬ÖÊÌ尢ùËصÄÃâÒßÔ­ÐÔϸ°ûËÀÍö£¬ÒÔÓÅ»¯ÃâÒß¼ì²éµã×è¶ÏÁÆ·¨µÄÖÎÁÆЧ¹û

Issue JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 2024, Volume 43 Issue 1

ÆÚ¿¯£º¡¶ÊµÑéÓëÁÙ´²°©Ö¢Ñо¿ÔÓÖ¾¡·£¨JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH£©£¬2024Ä꣬µÚ43¾í£¬µÚ1ÆÚ

Author Zhang Baoyuan / Li Ning / Gao Jiaming / Zhao Yuxi / Jiang Jun / Xie Shuang / Zhang Cuiping / Zhang Qingyu / Liu Leo / Wang Zaiqi / Ji Dongmei / Wu Lingying / Ren Ruibao

Cite this article as: [1]Zhang Baoyuan, Li Ning, Gao Jiaming, et al.Targeting of focal adhesion kinase enhances the immunogenic cell death of PEGylated liposome doxorubicin to optimize therapeutic responses of immune checkpoint blockade[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,2024,43(1).