Article
Oncology
Joel R. Eisner, Gregory M. Mayhew, James M. Davison, Kirk D. Beebe, Yoichiro Shibata, Yuelong Guo, Carol Farhangfar, Farhang Farhangfar, Joshua M. Uronis, Jeffrey M. Conroy, Michael Milburn, David Neil Hayes, Kathryn F. Mileham
Summary: The Piedmont study evaluated the application of a new 48-gene antifolate response signature (AF-PRS) in patients with locally advanced/metastatic non-squamous non-small cell lung cancer (NS-NSCLC) treated with PMX-PDC. The study found that AF-PRS can help identify patients who have a positive response to PMX-PDC treatment. This study provides clinical evidence supporting AF-PRS as a potential diagnostic test.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Giorgio Vittorio Scagliotti, Purvish Parikh, Joachim von Pawel, Bonne Biesma, Johan Vansteenkiste, Christian Manegold, Piotr Serwatowski, Ulrich Gatzemeier, Raghunadharao Digumarti, Mauro Zukin, Jin S. Lee, Anders Mellemgaard, Keunchil Park, Shehkar Patil, Janusz Rolski, Tuncay Goksel, Filippo de Marinis, Lorinda Simms, Katherine P. Sugarman, David Gandara
Summary: This phase III randomized study compared the efficacy of cisplatin plus gemcitabine and cisplatin plus pemetrexed in the treatment of advanced non-small-cell lung cancer (NSCLC). The results showed that cisplatin plus pemetrexed was noninferior to cisplatin plus gemcitabine in terms of overall survival. However, cisplatin plus pemetrexed showed superior survival in patients with adenocarcinoma and large-cell carcinoma histology, while cisplatin plus gemcitabine was more effective in patients with squamous cell histology. Cisplatin plus pemetrexed also had less adverse reactions and more convenient administration.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
You-Lung Chang, Yen-Fu Chen, Ying-Yin Chen, Shih-Chieh Chang, Cheng-Yu Chang, Yu-Feng Wei, Chung-Yu Chen
Summary: The study found that elevated expression of AEG-1 in NSCLC patients treated with pemetrexed may impact treatment response and survival. Liquid biopsy could serve as a predictive and prognostic biomarker for NSCLC patients.
APPLIED SCIENCES-BASEL
(2021)
Article
Multidisciplinary Sciences
Kentaro Jingushi, Masaya Aoki, Kazuhiro Ueda, Takahiro Kogaki, Masaya Tanimoto, Yuya Monoe, Masayuki Ando, Takuya Matsumoto, Kentaro Minami, Yuko Ueda, Kaori Kitae, Hiroaki Hase, Toshiyuki Nagata, Aya Harada-Takeda, Masatatsu Yamamoto, Kohichi Kawahara, Kazuhiro Tabata, Tatsuhiko Furukawa, Masami Sato, Kazutake Tsujikawa
Summary: The study reveals that high expression of ALKBH4 is associated with the progression of non-small-cell lung cancer, and knockdown of ALKBH4 can inhibit cancer cell proliferation and affect cell cycle and E2F1 expression. Patients with high ALKBH4 expression have a poor prognosis, indicating that ALKBH4 plays a crucial tumour-promoting role in NSCLC.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Dan Zhang, Haijing Liu, Zhennan Yi, Yuanyuan Lu, Yanyan Chen, Weiqiang Su, Huibing Lin, Zhihui Zhang, Wei Lei
Summary: Chemotherapy drug resistance is a major factor in the relapse and metastasis of NSCLC patients. The study identified TS as a potential predictive marker for PEM resistance and demonstrated that inhibition of the EGFR pathway can overcome drug resistance and suppress signaling pathways in PEM-resistant NSCLC cell lines.
Article
Oncology
Mihong Choi, Heung Tae, Ji-Youn Han, Geon Kook Lee, Soo-Hyun Lee, Kun Young Lim, Jungnam Joo, Hye Jin Won, Jin Soo Lee, Youngjoo Lee
Summary: In a single-arm phase II trial, pemetrexed showed modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression. The toxicity of pemetrexed was generally manageable, with most adverse events being grade 1 or 2.
CANCER RESEARCH AND TREATMENT
(2021)
Review
Health Care Sciences & Services
Michal Szczyrek, Paulina Bitkowska, Marta Jutrzenka, Janusz Milanowski
Summary: Lung cancer, a leading cause of global cancer-related deaths, is often diagnosed at advanced stages due to limited diagnostic possibilities. However, the use of miRNAs as diagnostic, predictive, and prognostic markers in non-small-cell lung cancer (NSCLC) has gained attention in recent years. Abnormal expression levels of miRNAs can detect NSCLC in its early asymptomatic stages, potentially improving clinical outcomes and serving as predictive factors for NSCLC treatment.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Yuzo Sato, Masaru Tomita, Tomoyoshi Soga, Atsushi Ochiai, Hideki Makinoshima
Summary: The study revealed that TYMS expression is elevated in drug-resistant cell lines compared to parental cell lines, knocking down TYMS can reduce drug resistance, while overexpression can increase resistance. Higher levels of dTMP in resistant cells suggest the importance of the nucleic acid-biosynthetic pathway for the efficacy of PMX.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marie Piecyk, Mouna Triki, Pierre-Alexandre Laval, Helena Dragic, Laura Cussonneau, Joelle Fauvre, Cedric Duret, Nicolas Aznar, Toufic Renno, Serge N. Manie, Cedric Chaveroux, Carole Ferraro-Peyret
Summary: The study found that in non-small cell lung cancer, the impact of pemetrexed (PEM) treatment on protein synthesis is regulated by glucose availability, with PEM inhibiting cell mass and translation when glucose is abundant, but its inhibitory effect is weakened at low glucose levels.
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)
Review
Oncology
Rafael Rosell, Anisha Jain, Jordi Codony-Servat, Eloisa Jantus-Lewintre, Blake Morrison, Jordi Barretina Ginesta, Maria Gonzalez-Cao
Summary: Lung oncogenesis relies on intracellular cysteine to overcome oxidative stress. Several mechanisms, such as the upregulation of cystine transporter SLC7A11, the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) and the activation of Extrinsic or Intrinsic apoptotic pathways, play important roles in the development of lung cancer. Moreover, the disruption of cystine availability and the involvement of exogenous cysteine/cystine and the transsulfuration pathway result in compromised CD8+ T cell function and evasion of immunotherapy, diminishing immune response and potentially reducing the effectiveness of immunotherapeutic interventions. Meanwhile, the breakthrough in KRAS G12C allele-specific inhibitors provides a potential therapeutic strategy for lung cancer treatment.
CANCER BIOLOGY & MEDICINE
(2023)
Review
Medicine, General & Internal
Ryota Ushio, Shuji Murakami, Haruhiro Saito
Summary: Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of non-small cell lung cancer patients. However, there is a lack of predictive biomarkers other than tumor PD-L1 expression. The search for biomarkers is urgent, and various biomarkers including PD-L1, tumor mutation burden, and blood biomarkers such as peripheral T-cell phenotype, neutrophil-to-lymphocyte ratio, interferon-gamma, and interleukin-8 have been identified. The development of composite markers and novel technologies may enable comprehensive analysis of multiple biomarkers.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Issei Sumiyoshi, Takahiro Okabe, Shinsaku Togo, Haruhi Takagi, Hiroaki Motomura, Yusuke Ochi, Naoko Shimada, Mizuki Haraguchi, Rina Shibayama, Yuichi Fujimoto, Junko Watanabe, Moe Iwai, Kotaro Kadoya, Shin-ichiro Iwakami, Kazuhisa Takahashi
Summary: This study investigated the clinical characteristics and predictive factors in patients with advanced NSq-NSCLC who underwent long-term PEM maintenance therapy. Results showed that ALC, NLR, and PD-1 expression are predictive biomarkers indirectly related to tumor immunity and can provide useful predictive information on the long-term response to PEM in patients with NSq-NSCLC.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Cell Biology
Jiun-Long Wang, Ying-Wei Lan, Yi-Ting Tsai, Ying-Cheng Chen, Theresa Staniczek, Yung-An Tsou, Chih-Ching Yen, Chuan-Mu Chen
Summary: The combination therapy of metformin and pemetrexed demonstrated antiproliferative effects by inducing cell cycle arrest in the S phase and exhibited antiangiogenic effects by inhibiting vascular structure formation. The research suggests that this combination treatment could be beneficial for clinical lung cancer therapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Yuki Shimizu, Koutaroh Okada, Jun Adachi, Yuichi Abe, Ryohei Narumi, Ken Uchibori, Noriko Yanagitani, Sumie Koike, Satoshi Takagi, Makoto Nishio, Naoya Fujita, Ryohei Katayama
Summary: This study found that glycogen synthase kinase 3 (GSK3) plays a crucial role in both intermediate and acquired resistance to lorlatinib in ALK-positive NSCLC. Inhibiting GSK3 can suppress the growth of resistant cells and make other resistant cells sensitive to lorlatinib.
NPJ PRECISION ONCOLOGY
(2022)