Review
Medicine, Research & Experimental
Xueting Wang, Xianhu Zeng, Dan Li, Chunrong Zhu, Xusheng Guo, Lingxin Feng, Zhuang Yu
Summary: DNA damage repair is closely associated with tumors, aging, and other factors. PARP inhibitors are being studied for their potential in cancer treatment. The discovery of gene connections in SCLC and the exploration of PARP inhibitors for SCLC treatment are important areas of research.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Oncology
Zofia Piotrowska, Daniel Shao-Weng Tan, Egbert F. Smit, Alexander I. Spira, Ross A. Soo, Danny Nguyen, Victor Ho-Fun Lee, James Chih-Hsin Yang, Vamsidhar Velcheti, John M. Wrangle, Mark A. Socinski, Marianna Koczywas, John E. Janik, Jeffrey Jones, Helena Alexandra Yu
Summary: This study demonstrates that Zipalertinib has encouraging antitumor activity in heavily pretreated patients with EGFR ex20ins-mutant NSCLC, with an acceptable safety profile and low frequency of high-grade diarrhea and rash.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Nobuaki Kobayashi, Seigo Katakura, Chisato Kamimaki, Kohei Somekawa, Nobuhiko Fukuda, Katsushi Tanaka, Keisuke Watanabe, Nobuyuki Horita, Yu Hara, Hongmei Piao, Takeshi Kaneko
Summary: This meta-analysis revealed significant differences in resistance mechanisms among different epidermal growth factor receptor tyrosine kinase inhibitors, such as T790M mutation. These differences should be considered when choosing treatment strategies.
Review
Pharmacology & Pharmacy
Manan P. Shah, Joel W. Neal
Summary: In the past two decades, advancements in molecular profiling and targeted therapies have significantly improved the treatment outcomes for patients with advanced non-small-cell lung cancer (NSCLC). EGFR gene mutations are commonly found in NSCLC, and first-generation targeted kinase inhibitors have improved survival rates. However, the emergence of resistance mechanisms has posed challenges to treatment. Current research focuses on developing drugs to overcome these resistance mechanisms.
Article
Oncology
Daichi Fujimoto, Hiroaki Akamatsu, Takeshi Morimoto, Kazushige Wakuda, Yuki Sato, Yoshitaka Kawa, Toshihide Yokoyama, Motohiro Tamiya, Ryota Hiraoka, Naoki Shingu, Hideki Ikeda, Akihiro Tamiya, Masaki Kanazu, Eisaku Miyauchi, Satoru Miura, Masaaki Yanai, Makiko Yomota, Ryotaro Morinaga, Takashi Yokoi, Akito Hata, Hidekazu Suzuki, Hirotaka Matsumoto, Shinya Sakata, Naoki Furuya, Yuhei Harutani, Ichiro Nakachi, Ayumu Otsuki, Shinya Uematsu, Satoshi Hara, Keiki Yokoo, Takeya Sugimoto, Nobuyuki Yamamoto
Summary: This study aimed to determine the incidence and clinical course of histologic transformation (HT) in lung cancer patients with epidermal growth factor receptor (EGFR) mutations. The study found that approximately 3% of EGFR-mutated patients developed HT after acquiring resistance to EGFR-tyrosine kinase inhibitors (TKIs). There was no significant difference in survival between patients with transformation to high-grade neuroendocrine carcinoma and those with transformation to another subtype of non-small cell lung cancer. Cytotoxic agents were likely to be effective in patients with HT, while the effectiveness of immune checkpoint inhibitors was limited.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Jin Wang, Shuai Tan, Ping-Ping Yan, Xue Xiao, Hao Zhang, San-Qi Zhang, Wei Li, Yong-Xiao Cao, Hong-Ying Wang
Summary: Z25h is a potential therapeutic drug candidate for non-small cell lung adenocarcinoma, which can inhibit the growth and survival of lung cancer cells by suppressing the EGFR signaling pathway and inducing apoptosis.
Review
Biochemistry & Molecular Biology
Shin-ichi Hirano, Haru Yamamoto, Yusuke Ichikawa, Bunpei Sato, Yoshiyasu Takefuji, Fumitake Satoh
Summary: H-2, an inert molecule, has been shown to effectively scavenge hydroxyl radicals responsible for DNA mutations, and is reported to be beneficial in diseases caused by oxidative stress and chronic inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Qiang Lu, Yunfeng Ni, Wuping Wang, Lei Wang, Tao Jiang, Lei Shang
Summary: The downregulation of DNM3 in patients with lung cancer accelerates the proliferative and metastatic abilities of cancer cells. The interaction of DNM3 with GBR2 suppresses STAT3 activation, and potential treatment strategies may involve the use of the c-MET inhibitor crizotinib.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Cristina Minnelli, Laura Cianfruglia, Emiliano Laudadio, Giovanna Mobbili, Roberta Galeazzi, Tatiana Armeni
Summary: The study evaluated the effect of EGCG on inhibiting NSCLC cell lines with EGFR activating mutations, demonstrating that EGCG polyphenol can inhibit cell proliferation and migration with varying efficacy and mechanisms. These findings may be of interest for evaluating the use of EGCG as an adjunct to NSCLC therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Juliann Chmielecki, Jhanelle E. Gray, Ying Cheng, Yuichiro Ohe, Fumio Imamura, Byoung Chul Cho, Meng-Chih Lin, Margarita Majem, Riyaz Shah, Yuri Rukazenkov, Alexander Todd, Aleksandra Markovets, J. Carl Barrett, Ryan J. Hartmaier, Suresh S. Ramalingam
Summary: By sequencing circulating tumor DNA in patients from the FLAURA trial, this study identifies MET amplification and EGFR C797S mutation as the most frequent acquired resistance mechanisms to first-line osimertinib.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Zhe Liu, Liang Ma, Yiming Sun, Wenying Yu, Xue Wang
Summary: The study demonstrated that the STAT3/ZEB1 axis is critical in gefitinib resistance in lung cancer, and a new potential therapeutic strategy targeting STAT3 has been identified with the inhibitor LL1. LL1 was shown to sensitize resistant cells to gefitinib by depleting STAT3 activity and blocking its signaling pathways, with little observed toxicity in animal models, indicating it could be a chemotherapeutic adjuvant for gefitinib resistance in NSCLC.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Jordi Codony-Servat, Silvia Garcia-Roman, Miguel Angel Molina-Vila, Jordi Bertran-Alamillo, Santiago Viteri, Erik d'Hondt, Rafael Rosell
Summary: The study indicates that anti-EGF antibodies generated by vaccination can enhance the antitumor activity of TKIs in ALK and RET-positive NSCLC cell lines, improving the efficacy of kinase inhibitors and delaying the emergence of resistant clones. This suggests that combining EGF vaccine with ALK and RET TKIs in clinical trials may be beneficial for advanced NSCLC patients with EML4-ALK and CCDC6-RET rearrangements.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Biology
Xiaolong Tang, Lizhi Cheng, Guo Li, Yong-Ming Yan, Fengting Su, Dan-Ling Huang, Shuping Zhang, Zuojun Liu, Minxian Qian, Ji Li, Yong-Xian Cheng, Baohua Liu
Summary: The small molecule compound D6 demonstrates promising efficacy in treating EGFR-TKI resistant NSCLC by targeting the protein-protein interaction between HSP90 and T790M-EGFR, offering a potential alternative strategy to overcome drug resistance.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Meng-di Dai, Yue-liang Wang, Jun Fan, Yang Dai, Yin-chun Ji, Yi-ming Sun, Xia Peng, Lan-lan Li, Yu-ming Wang, Wen-hu Duan, Jian Ding, Jing Ai
Summary: DW14383 is a promising selective irreversible pan-FGFR inhibitor with pan-tumor spectrum potential in FGFR1-4 aberrant cancers, which has the potential to overcome compensatory activation among FGFR1-4.
ACTA PHARMACOLOGICA SINICA
(2021)
Review
Oncology
Lihui Liu, Chao Wang, Sini Li, Hua Bai, Jie Wang
Summary: The tumor immune microenvironment (TIME) in EGFR-mutated NSCLC differs from non-mutated NSCLC, leading to poor response to ICIs. TIME in EGFR-mutated NSCLC changes during EGFR-TKI treatment. In EGFR-TKI-resistant tumors, there is an increase in immunosuppressive cells, decrease in immune-activated cells, and secretion of negative immune regulatory factors, resulting in immune escape and eventual resistance to EGFR-TKIs.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Alessandra Guido, Dajana Cuicchi, Paolo Castellucci, Francesco Cellini, Francesca Di Fabio, Fabiola Lorena Rojas Llimpe, Lidia Strigari, Milly Buwenge, Savino Cilla, Francesco Deodato, Gabriella Macchia, Erika Galietta, Rita Golfieri, Andrea Ardizzoni, Rocco Maurizio Zagari, Stefano Fanti, Gilberto Poggioli, Lorenzo Fuccio, Alessio G. Morganti
Summary: This study aimed to evaluate the pathological complete response rate of locally advanced rectal cancer after high-dose neoadjuvant chemoradiation based on FDG-PET/CT. The results showed that dose escalation on the target in the final phase of chemoradiation is well tolerated and can provide a high pathological complete response rate.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Pharmacology & Pharmacy
Motahareh Mortazavi, Elaheh Raufi, Tahereh Damghani, Mehdi Khoshneviszadeh, Najmeh Edraki, Masoomeh Eskandari, Elisa Giovannetti, Godefridus J. Peters, Somayeh Pirhadi, Omidreza Firuzi
Summary: c-Met receptor tyrosine kinase is an important therapeutic target in pancreatic cancer. A virtual screening and experimental testing were conducted to identify potential c-Met inhibitors from a compound library. The most active compound, PhTH, demonstrated antiproliferative effects against PDAC cells, induced apoptosis, and inhibited c-Met activity. Molecular docking and simulation analysis confirmed the strong interactions between PhTH and c-Met kinase domain. These findings suggest the potential of PhTH and other compounds as c-Met inhibitors in the treatment of PDAC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Oncology
M. Houweling, U. K. Abdul, C. Brahm, T. Lagerweij, S. Heukelom, P. W. Koken, R. Honeywell, L. E. Wedekind, G. J. Peters, H. Verheul, P. Sminia, D. Noske, T. Wurdinger, B. A. Westerman
Summary: This study investigated the radio-sensitizing effect of MEK inhibitor PD0325901 in in vitro and in vivo models of glioblastoma (GBM). The results showed that both MEK inhibitors had an in vitro radio-sensitizing effect, but no significant interaction between PD0325901 MEK inhibition and irradiation was observed in in vivo experiments.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Federica Borea, Marika A. Franczak, Maria Garcia, Matteo Perrino, Nadia Cordua, Ryszard T. Smolenski, Godefridus J. Peters, Rafal Dziadziuszko, Armando Santoro, Paolo A. Zucali, Elisa Giovannetti
Summary: Malignant Pleural Mesothelioma (MPM) is a rare neoplasm that is usually diagnosed at an advanced stage and requires systemic treatment due to its ineligibility for radical surgery. Chemotherapy has been the standard treatment for 20 years until immune checkpoint inhibitors were introduced. However, the prognosis remains poor, and targeted therapies for MPM have mostly failed in clinical trials. This review aims to explore the potential reasons for treatment failures and determine the need for further research in this area.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marika A. Franczak, Oliwia Krol, Gabriela Harasim, Agata Jedrzejewska, Nadia Zaffaroni, Carlotta Granchi, Filippo Minutolo, Amir Avan, Elisa Giovannetti, Ryszard T. Smolenski, Godefridus J. Peters
Summary: Malignant mesothelioma (MM) is a highly aggressive and resistant tumor. In this study, the cytotoxicity of new inhibitors of glucose transporter type 1 (GLUT-1) and lactate dehydrogenase-A (LDH-A) in relation to ATP/NAD+ metabolism, glycolysis and mitochondrial respiration was investigated. The inhibitors showed cytotoxicity in MM cells, associated with a decrease in ATP and NAD+, and were most effective in cells with the highest metabolic modulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Kemel Arafet, Laura Scalvini, Francesca Galvani, Sergio Marti, Vicent Moliner, Marco Mor, Alessio Lodola
Summary: Targeted covalent inhibitors show potential for drug discovery, specifically for kinases. Targeting the catalytic lysine of EGFR has gained attention for overcoming resistance caused by the C797S mutation. Sulfonyl fluoride derivatives have been reported as inhibitors of EGFRL858R/T790M/C797S through sulfonylation of Lys745. However, the mechanism behind this process is poorly understood.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Francesca Galvani, Daniele Pala, Alberto Cuzzolin, Laura Scalvini, Alessio Lodola, Marco Mor, Andrea Rizzi
Summary: In this study, two metadynamics protocols were used to estimate the residence times of muscarinic M3 receptor antagonists. The results showed that both computational methods were able to accurately rank compounds according to their experimental residence times.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Oncology
Yan Zhou, Yizhen Guo, Maoxin Ran, Wenying Shan, Carlotta Granchi, Elisa Giovannetti, Filippo Minutolo, Godefridus J. Peters, Kin Yip Tam
Summary: This study investigated the anticancer effects of combined inhibition of PDK1 and LDHA in LUAD and its underlying mechanisms. The results showed that the combination of a PDK1 inhibitor and a LDHA inhibitor could synergistically inhibit LUAD growth and suppress tumor growth in vivo. This combination also inhibited cellular migration and colony formation, inducing mitochondrial depolarization and apoptosis in LUAD cells.
Letter
Oncology
Lenka N. C. Boyd, Mahsoem Ali, Jisce R. Puik, Laura L. Meijer, Tessa Y. S. Le Large, Hanneke W. M. van Laarhoven, Elisa Giovannetti, Geert Kazemier
CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Mahrou Vahabi, Annalisa Comandatore, Marika A. Franczak, Ryszard T. Smolenski, Godefridus J. Peters, Luca Morelli, Elisa Giovannetti
Summary: Exosomes play a crucial role in intercellular communication and can influence cancer cell behavior and response to treatment. They can transport glycolytic enzymes, leading to altered glucose metabolism and increased tumor progression, survival, immune evasion, and drug resistance. Understanding exosome-mediated cell-to-cell communication may open new therapeutic avenues and facilitate biomarker development, and combining exosome-based-targeted therapies with existing treatments holds promise in overcoming resistance and improving cancer treatment outcomes.
CYTOKINE & GROWTH FACTOR REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Lars Petter Jordheim, Caius G. Radu, Godefridus J. Peters
Summary: This article introduces the scientific program of the 20th biennial symposium on Purine and Pyrimidine metabolism organized by the Purine and Pyrimidine Society (PPS) in June 2023. The symposium covers various topics including inborn errors, cancer, immunity, enzymatic reactions, and drug development, and is presented in 9 sessions over three days.
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
(2023)
Article
Oncology
Alireza Asadnia, Elham Nazari, Ladan Goshayeshi, Nima Zafari, Mehrdad Moetamani-Ahmadi, Lena Goshayeshi, Haneih Azari, Ghazaleh Pourali, Ghazaleh Khalili-Tanha, Mohammad Reza Abbaszadegan, Fatemeh Khojasteh-Leylakoohi, Mohammadjavad Bazyari, Mir Salar Kahaei, Elnaz Ghorbani, Majid Khazaei, Seyed Mahdi Hassanian, Ibrahim Saeed Gataa, Mohammad Ali Kiani, Godefridus J. Peters, Gordon A. Ferns, Jyotsna Batra, Alfred King-yin Lam, Elisa Giovannetti, Amir Avan
Summary: This study identified genetic variants and differentially expressed genes in colorectal cancer patients using genome-wide DNA and RNA sequencing. ASPHD1 and ZBTB12 genes were identified as potential prognostic markers, and two novel genetic variants were found to potentially regulate gene expression. These findings provide a proof of concept for the evaluation of emerging biomarkers in colorectal cancer.
Editorial Material
Cell Biology
Andrea Cavazzoni, Graziana Digiacomo
Article
Biochemistry & Molecular Biology
Nabeel Merali, Tarak Chouari, Julien Terroire, Maria-Danae Jessel, Daniel S. K. Liu, James-Halle Smith, Tyler Wooldridge, Tony Dhillon, Jose I. Jimenez, Jonathan Krell, Keith J. Roberts, Timothy A. Rockall, Eirini Velliou, Shivan Sivakumar, Elisa Giovannetti, Ayse Demirkan, Nicola E. Annels, Adam E. Frampton
Summary: The bile microbiome plays an important role in pancreatic ductal adenocarcinoma (PDAC) and can distinguish malignant tumors from benign ones. It was found that the composition of the bile microbiome is altered in patients with PDAC, suggesting that these microbial changes could potentially serve as diagnostic and prognostic biomarkers for PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)