Article
Biochemistry & Molecular Biology
Zekai Huang, Markus Kaller, Heiko Hermeking
Summary: miR-34a and miR-34b/c, as direct targets of p53, play a crucial role in the tumor suppressive effects of p53. Inactivating miR-34a and/or miR-34b/c in colorectal cancer cell line HCT116 had significant effects on proliferation, migration, invasion, chemosensitivity, autophagy, and apoptosis. The concomitant deletion of miR-34a and miR-34b/c resulted in EMT signature enrichment, impaired gene repression by the p53-DREAM pathway, and elevated autophagy. A gene signature upregulated in cells with combined inactivation of miR-34a and miR-34b/c was associated with invasive colon cancer subtype CMS4, poor overall survival in CRC patients, and 5-FU resistance in CRC cell lines.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Oncology
Elena Michaels, Christine M. Bestvina
Summary: The MET pathway can be activated by various mechanisms in NSCLC, including mutations and amplifications. Detection methods for MET alterations include RNA-based NGS and FISH. Newer selective MET TKIs have shown improved efficacy, and MET amplification is a common resistance mechanism to EGFR inhibition.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Gordana Supic, Debora Stefik, Nemanja Ivkovic, Ahmad Sami, Katarina Zeljic, Sasa Jovic, Ruzica Kozomara, Danilo Vojvodic, Srboljub Stosic
Summary: miR-34b/c hypermethylation and low miR-34b expression may promote the progression of HPV-negative OSCC and predict a poor prognosis, providing evidence for miR-34b/c as a promising biomarker and therapeutic target for OSCC in the future.
SCIENTIFIC REPORTS
(2022)
Article
Plant Sciences
Rui Wang, Zhiyin Deng, Zhiming Zhu, Juanjuan Wang, Xiaobing Yang, Mengfei Xu, Xi Wang, Qing Tang, Qichun Zhou, Xinliang Wan, Wanyin Wu, Sumei Wang
Summary: Kaempferol inhibits non-small cell lung cancer (NSCLC) cell proliferation and promotes autophagy-induced cell death. It inhibits Met protein and mRNA expression, as well as the PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism of kaempferol in inhibiting NSCLC through autophagy regulation of the Met and PI3K/AKT/mTOR signaling pathway.
Article
Chemistry, Medicinal
Chaofan Wang, Xiaoyun Lu
Summary: MET is a promising drug target for the treatment of MET-dependent diseases, especially NSCLC. Small molecule MET inhibitors with three types of binding modes have been developed. This review provides an overview of MET's structural features, activation mechanism, dysregulation pathway, and the development strategies of MET inhibitors, as well as the acquired resistance mechanisms. These insights will accelerate the discovery of new generation MET inhibitors to overcome clinical acquired resistance.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Xiaolei Yao, Hui Shen, Qinghua Peng, Jingsheng Yu
Summary: This study found a positive correlation between p53 and miR-129 in RB, where miR-129 directly targeted MDM2/4 to inhibit expression, counteracting MDM2/4-mediated p53 signaling suppression and modulating RB cell proliferation and apoptosis.
Article
Oncology
Yu-Ra Choi, Eun Hye Kang, Sunshin Kim, Seog-Yun Park, Ji-Youn Han, Youngjoo Lee
Summary: This study evaluated the efficacy of single MET inhibition in EGFR-mutant and MET-amplified lung cancer and found that it produced a short-lived response. Further research on novel combination therapy schedules is needed to achieve long-lasting efficacy with less toxicity.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cell Biology
Dong Ha Kim, Hyojeong Park, Yun Jung Choi, Myoung-Hee Kang, Tae-Keun Kim, Chan-Gi Pack, Chang-Min Choi, Jae Cheol Lee, Jin Kyung Rho
Summary: Exosomal miR-1260b promotes angiogenesis in HUVECs and metastasis in NSCLC by targeting HIPK2, and may serve as a potential prognostic marker for lung cancer.
CELL DEATH & DISEASE
(2021)
Article
Integrative & Complementary Medicine
Xinhua Lu, Chenyang Xu, Zhexuan Xu, Chunya Lu, Rui Yang, Furui Zhang, Guojun Zhang
Summary: Piperlongumine (PL) extracted from the roots of piperaceae plant inhibits proliferation and induces apoptosis of A549 and H1299 non-small cell lung cancer cells by upregulating miR-34b-3p and modulating the TGFBR1 signaling pathway.
BMC COMPLEMENTARY MEDICINE AND THERAPIES
(2021)
Review
Oncology
Mandy Sakamoto, Tejas Patil
Summary: Targeting the MET pathway is an important approach in the treatment of advanced NSCLC, as it plays a role in both primary oncogenesis and acquired resistance. However, the various mechanisms of MET pathway activation can complicate diagnosis and treatment. Recent developments in MET-directed therapies show promising results. This review summarizes the biology, mechanisms, diagnostic challenges, importance in acquired resistance, and novel treatment strategies of MET in advanced NSCLC.
Article
Cell Biology
Jianhao Xu, Liwei Ni, Fenglun Zhao, Xiaoxiao Dai, Jialong Tao, Jia Pan, Aiming Shi, Zhu Shen, Cunjin Su, Yusong Zhang
Summary: This study identified that hsa_circ_0002874 acts as a sponge for miR1273f targeting MDM2/P53, influencing apoptosis and paclitaxel resistance in non-small cell lung cancer. The findings suggest that downregulation of hsa_circ_0002874 could reverse PTX resistance by regulating the miR1273f/MDM2/P53 signaling pathway, indicating its potential as a marker for drug resistance in NSCLC.
Article
Oncology
Jian Huang, Fanglin Tian, Ying Song, Mengru Cao, Shi Yan, Xiuwen Lan, Yimeng Cui, Yaowen Cui, Yue Cui, Dexin Jia, Li Cai, Ying Xing, Xin Wang
Summary: The study demonstrated that EHD1 plays a crucial role in non-small cell lung cancer, regulating the glycolysis pathway through the Wnt/beta-catenin signaling, promoting aerobic glycolysis and proliferation. These findings suggest a potential therapeutic target for NSCLC.
Review
Biochemistry & Molecular Biology
Calogera Claudia Spagnolo, Giuliana Ciappina, Elisa Giovannetti, Andrea Squeri, Barbara Granata, Chiara Lazzari, Giulia Pretelli, Giulia Pasello, Mariacarmela Santarpia
Summary: In recent years, the development of therapeutic agents targeting actionable oncogenic drivers in metastatic non-small cell lung cancer (NSCLC) has increased. Selective inhibitors, such as tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have shown promising results in patients with MET deregulation, specifically exon 14 skipping mutations or MET amplification. This review provides an overview of MET signaling pathways, oncogenic alterations, laboratory techniques for detection, clinical data and ongoing studies on MET inhibitors, resistance mechanisms, and potential strategies for improving outcomes in MET-exon 14-altered NSCLC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Liangping Li, Wenqing Du, Hui Wang, Yufei Zhao, Zetian Huang, Yan Peng, Shulan Zeng, Guohai Zhang
Summary: We report two p53 activators, MX-C2 and MX-C3, with high efficiency and low toxicity, which have the potential for treating oncogene-driven tumors and exhibit broad antitumor activity in NSCLC cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Pharmacology & Pharmacy
Edward B. Garon, Paige Brodrick
Summary: The tyrosine kinase receptor mesenchymal epithelial transition (MET) plays a role in non-small cell lung cancer (NSCLC) and abnormal activation may contribute to oncogenesis. MET overexpression, amplification, or mutation as therapeutic targets are of interest, particularly MET exon 14 skipping mutations which have shown significant responses to MET inhibitors.