Article
Oncology
Francisco Exposito, Miriam Redrado, Maeva Houry, Katherine Hastings, Magdalena Molero-Abraham, Teresa Lozano, Jose Luis Solorzano, Julian Sanz-Ortega, Vera Adradas, Ramon Amat, Esther Redin, Sergio Leon, Naroa Legarra, Javier Garcia, Diego Serrano, Karmele Valencia, Camila Robles-Oteiza, Giorgia Foggetti, Nerea Otegui, Enriqueta Felip, Juan J. Lasarte, Luis Paz-Ares, Jon Zugazagoitia, Katerina Politi, Luis Montuenga, Alfonso Calvo
Summary: Immunotherapy resistance in non-small cell lung cancer (NSCLC) can be attributed to an immunosuppressive microenvironment created by genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression. PTEN-low tumors are associated with higher levels of immune checkpoint proteins and poorer response to immunotherapy. Preclinical models demonstrate that PTEN loss promotes metastasis and fibrosis, and facilitates the conversion of immune cells into immunosuppressive regulatory T cells (Treg). However, targeting PTEN loss-mediated immunosuppression can reverse immunotherapy resistance in NSCLC.
Article
Biochemistry & Molecular Biology
Sathan Raj Natarajan, Lavanya Ponnusamy, Ravi Manoharan
Summary: MARK2 and MARK4 are upregulated in non-small cell lung cancer (NSCLC) and associated with advanced stages and low survival rate. Inhibition of MARK2/4 suppresses aerobic glycolysis and cell growth in NSCLC cells, exerting its effect through the regulation of the mTOR/HIF-1α pathway and AMPK activity.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Yingchen Xia, Chunyan He, Zhi Hu, Zhichao Wu, Yin Hui, Yuan-yuan Liu, Chuanyong Mu, Jianhua Zha
Summary: This study investigates the expression and biological function of YME1L in NSCLC. The results show that YME1L is upregulated in NSCLC tissues and cells, and its knockdown or knockout suppresses cell growth, migration, and induces apoptosis. YME1L dysregulation leads to mitochondrial dysfunction, including depolarization, ROS accumulation, and ATP depletion. Conversely, overexpression of YME1L promotes NSCLC cell proliferation and motility. Akt-S6K1 phosphorylation is affected by YME1L modulation, and YME1L KO-induced anti-NSCLC cell activity can be reversed by Akt1 activation. In vivo, YME1L knockdown inhibits NSCLC xenograft growth. Thus, YME1L has a pro-tumorigenic function in NSCLC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Oncology
Claudia Dominici, Nicolas Sgarioto, Zhenbao Yu, Laura Sesma-Sanz, Jean-Yves Masson, Stephane Richard, Noel J. -M. Raynal
Summary: The study finds that PARP inhibitors have a strong synergistic interaction with Type I PRMT inhibitors in NSCLC cells, significantly reducing cell viability. Re-introduction of MTAP decreases the sensitivity of the combination therapy in A549 cells, while the combination therapy leads to increased DNA damage and decreased cell viability. The combination therapy is also effective in PARPi resistant ovarian cancer cells, indicating the potential clinical impact of type I PRMT inhibitors in mitigating PARPi resistance.
CLINICAL EPIGENETICS
(2021)
Review
Oncology
Zihan Quan, Yang Yang, Hongmei Zheng, Yuting Zhan, Jiadi Luo, Yue Ning, Songqing Fan
Summary: The discovery of immune checkpoints has provided new clues for cancer treatments. Immunotherapy targeting PD-1/PD-L1 has been widely used in various tumor treatments, but side effects and drug resistance are challenges. The PI3K/AKT/mTOR pathway may regulate PD-L1 expression through post-transcription and translation. The interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway affects both tumor cells and the tumor immune microenvironment. Combination therapy shows great research value for better therapeutic effect and quality of survival. This review summarizes the interaction between PD-1/PD-L1 and the PI3K/AKT/mTOR pathway in NSCLC and its clinical implications, broadening the therapies for NSCLC.
Article
Biochemistry & Molecular Biology
Xiaoling Zhang, Hao Liu, Haidong Wang, Rongjie Zhao, Qian Lu, Yunlong Liu, Yicheng Han, Hongming Pan, Weidong Han
Summary: This study found that b3galt5 is highly expressed in hepatocellular carcinoma (HCC) and associated with poor prognosis. It promotes the proliferation and survival of HCC cells and activates the mTOR/p70s6k pathway to enhance glycolysis through O-linked glycosylation modification. Inhibition of p70s6k reduces glycolysis in b3galt5-overexpressing cells. This study uncovers a novel mechanism and potential therapy target for HCC.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Oncology
Hao Liu, Li-Hong Chen, Zhi-Hui Zhang, Ning Wang, Si-Hui Zhuang, Hao Chen, Jin Du, Li-Juan Pang, Yan Qi
Summary: This study reported two cases of small cell transformation of non-small cell lung cancer (NSCLC) after targeted therapy or immunotherapy. The transformation to small cell lung cancer is a potential mechanism of NSCLC resistance to targeted therapy or immunotherapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Wei Zhang, Chunai Gong, Ziqiang Chen, Ming Li, Yuping Li, Jing Gao
Summary: The research integrates cancer cell membranes with switchable peptide-based charge-reversal liposome membranes to create a hybrid nanoplatform for smart drug delivery. This platform demonstrates excellent drug release and targeted therapy effects triggered by pH and redox, with potential therapeutic applications for non-small cell lung cancer.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Senxia Zhao, Yibin Li, Gang Li, Juanping Ye, Rong Wang, Xiaoting Zhang, Fei Li, Chang Gao, Junbiao Li, Jie Jiang, Yanjun Mi
Summary: This study demonstrated that the PI3K/mTOR inhibitor VS-5584 effectively suppressed the growth of NSCLC cells by inhibiting cell proliferation, inducing apoptosis, and causing cell cycle arrest. Treatment with VS-5584 also resulted in an increase in intracellular reactive oxygen species (ROS) levels, and the use of an ROS inhibitor reduced apoptosis. Furthermore, VS-5584 affected multiple genes and biological processes, including cell cycle regulation and apoptosis pathways, and exhibited a synergistic effect when combined with a PLK1 inhibitor in inhibiting NSCLC cell growth. These findings suggest that VS-5584 has potential as a therapeutic strategy for NSCLC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Senxia Zhao, Yibin Li, Gang Li, Juanping Ye, Rong Wang, Xiaoting Zhang, Fei Li, Chang Gao, Junbiao Li, Jie Jiang, Yanjun Mi
Summary: The PI3K/mTOR inhibitor VS-5584 effectively inhibits the growth of NSCLC cells both in vitro and in vivo by suppressing proliferation, inducing apoptosis and cell cycle arrest. It also alters gene expression related to apoptosis and cell cycle regulation. Furthermore, combined treatment with VS-5584 and PLK1 inhibitor NMS-P937 shows synergistic inhibitory activity against NSCLC cell growth. These findings suggest that VS-5584 has potential as a therapeutic strategy for NSCLC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Edwin Roger Parra, Jiexin Zhang, Mei Jiang, Auriole Tamegnon, Renganayaki Krishna Pandurengan, Carmen Behrens, Luisa Solis, Cara Haymaker, John Victor Heymach, Cesar Moran, Jack J. Lee, Don Gibbons, Ignacio Ivan Wistuba
Summary: Studying the cellular geographic distribution in non-small cell lung cancer is crucial for understanding the roles of cell populations in this tumor. This study characterizes the spatial cellular distribution of immune cell populations and their associations with clinicopathologic variables and outcomes. The results show two cellular distribution patterns related to immunoprotective and immunosuppressive cells, respectively, and reveal the proximity of immune checkpoint-expressing T-cells to malignant cells. The combination of cellular distribution patterns and distances can identify different tumor groups and predict survival.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Si Yeon Song, Ji Hye Park, So-Jung Park, In-Cheol Kang, Hwa-Seung Yoo
Summary: This study investigated the therapeutic effect of combining HAD-B1 and afatinib in NSCLC with gefitinib resistance. The results demonstrated that the combination treatment significantly inhibited tumor cell proliferation, induced apoptosis, and had a synergistic effect on regulating signaling pathways.
INTEGRATIVE CANCER THERAPIES
(2022)
Review
Oncology
Ichidai Tanaka, Junji Koyama, Hideyuki Itoigawa, Shunsaku Hayai, Masahiro Morise
Summary: Immune checkpoint inhibitors (ICIs) are considered standard treatment for advanced non-small cell lung cancer (NSCLC) with no viable treatment options. However, NSCLC tumors with mutations in LKB1 and/or KEAP1 have shown reduced response to ICIs due to immunosuppressed phenotypes caused by metabolic alterations in glycolysis and glutaminolysis. The consumption of glucose and glutamine by tumor cells leads to immunosuppression and resistance to ICI therapies. This review discusses current therapeutic strategies and ongoing trials targeting these metabolic alterations in NSCLC, in order to improve prognosis.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Hongwei Lin, Yanjun Gao, Kang Sun, Qian Zhang, Yujuan Li, Min Chen, Faguang Jin
Summary: Recent advances in cancer research have revealed a close relationship between mitochondrial dysfunction and cancer development. This study found that COA3 is overexpressed in non-small cell lung cancer (NSCLC) and is associated with lymph node metastasis and poor survival. Silencing COA3 can weaken the migration and invasiveness of NSCLC cells, while forced expression of COA3 enhances their migration and invasiveness. Mechanistically, aerobic glycolysis, induced by mitochondrial fragmentation mediated by DRP1 phosphorylation, contributes to COA3-promoted NSCLC metastasis.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Yuxi Zhang, Yi Wang, Yanping Li, Cong Huang, Xiaoqian Xiao, Zhanqiong Zhong, Jingyi Tang, Haolan Lu, Yibei Tang, Jiahui Yang
Summary: In this study, it is shown that dihydroartemisinin (DHA) and artemisinin (AS) inhibit aerobic glycolysis in non-small cell lung cancer (NSCLC) cells through the ERK/c-Myc pathway, leading to the inhibition of tumor growth. This study expands our knowledge of artemisinin derivatives in regulating tumor glucose metabolism and provides a potential strategy for lung cancer therapy.
BIOCHEMICAL PHARMACOLOGY
(2022)