Article
Oncology
Alexis B. Cortot, Anne Madroszyk, Etienne Giroux-Leprieur, Olivier Molinier, Elisabeth Quoix, Henri Berard, Josiane Otto, Isabelle Rault, Denis Moro-Sibilot, Judith Raimbourg, Elodie Amour, Franck Morin, Jose Hureaux, Lionel Moreau, Didier Debieuvre, Hugues Morel, Aldo Renault, Eric Pichon, Benjamin Huret, Sandrine Charpentier, Marc G. Denis, Jacques Cadranel
Summary: The addition of cetuximab to afatinib in the treatment of treatment-naive advanced EGFR-mutant NSCLC did not show any significant improvement in efficacy, suggesting that further investigation into this combination therapy may not be warranted.
CLINICAL CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Chie Morita, Tatsuya Yoshida, Masayuki Shirasawa, Ken Masuda, Yuji Matsumoto, Yuki Shinno, Shigehiro Yagishita, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Noriko Motoi, Yasushi Yatabe, Yuichiro Ohe
Summary: Patients with Exon20ins mutations and major mutations had similar clinical characteristics, but Exon20ins patients had less satisfactory clinical outcomes compared to M-mut patients.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Shidan Wang, Ruichen Rong, Donghan M. Yang, Junya Fujimoto, Justin A. Bishop, Shirley Yan, Ling Cai, Carmen Behrens, Lynne D. Berry, Clare Wilhelm, Dara Aisner, Lynette Sholl, Bruce E. Johnson, David J. Kwiatkowski, Ignacio I. Wistuba, Paul A. Bunn, John Minna, Guanghu Xiao, Mark G. Kris, Yang Xie
Summary: This study developed a prediction model for survival benefit from EGFR TKI therapy in lung adenocarcinoma patients with EGFR-sensitizing mutations, based on the quantification of tumor microenvironment features. The model was validated in an independent cohort and showed that EGFR TKI treatment prolonged survival in the predicted-to-benefit group but not in the predicted-not-to-benefit group. Tumor-tumor interaction image features were positively correlated with EGFR TKI survival benefit, while tumor-stroma interaction was negatively correlated.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Oncology
Ying Cheng, Yong He, Wei Li, He-long Zhang, Qing Zhou, Buhai Wang, Chunling Liu, Andrew Walding, Matilde Saggese, Xiangning Huang, Minhao Fan, Jia Wang, Suresh S. Ramalingam
Summary: The FLAURA China study evaluated the efficacy of first-line osimertinib in Chinese patients with EGFRm advanced NSCLC, showing significant improvements in PFS and OS compared to comparator EGFR TKIs. Safety data were consistent with the known safety profile of osimertinib.
Article
Oncology
Lecia V. Sequist, James Chih-Hsin Yang, Nobuyuki Yamamoto, Kenneth O'Byrne, Vera Hirsh, Tony Mok, Sarayut Lucien Geater, Sergey Orlov, Chun-Ming Tsai, Michael Boyer, Wu-Chou Su, Jaafar Bennouna, Terufumi Kato, Vera Gorbunova, Ki Hyeong Lee, Riyaz Shah, Dan Massey, Victoria Zazulina, Mehdi Shahidi, Martin Schuler
Summary: The study compared the efficacy of chemotherapy with afatinib in the treatment of EGFR-mutated lung adenocarcinoma. Results showed that afatinib prolonged progression-free survival and improved the quality of life for patients, when compared with chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Wen-Zhao Zhong, Hong-Hong Yan, Ke-Neng Chen, Chun Chen, Chun-Dong Gu, Jun Wang, Xue-Ning Yang, Wei-Min Mao, Qun Wang, Gui-Bin Qiao, Ying Cheng, Lin Xu, Chang-Li Wang, Ming-Wei Chen, Xiao-Zheng Kang, Wan-Pu Yan, Ri-Qiang Liao, Jin-Ji Yang, Xu-Chao Zhang, Si-Yang Liu, Qing Zhou, Yi-Long Wu
Summary: A study found that neoadjuvant erlotinib treatment improved progression-free survival (PFS) for patients with EGFR sensibility mutations and R0 resected stage IIIA-N2 non-small cell lung cancer (NSCLC) compared to chemotherapy.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Multidisciplinary Sciences
Chia- Shen, Chi-Lu Chiang, Tsu-Hui Shiao, Yung-Hung Luo, Heng-Sheng Chao, Hsu-Ching Huang, Chao-Hua Chiu
Summary: Detection of driver gene mutations is crucial in advanced NSCLC. The cobas EGFR mutation test has limitations due to its primer design, while next-generation sequencing-based assay provides a higher mutation detection coverage. Comprehensive genomic profiling can identify EGFR mutations missed by the cobas test and offers significant benefits to patients with NSCLC.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Jian-Gan Ren, Bowen Xing, Kaoshen Lv, Rachel A. O'Keefe, Mengfang Wu, Ruoxing Wang, Kaylyn M. Bauer, Arevik Ghazaryan, George M. Burslem, Jing Zhang, Ryan M. O'Connell, Vinodh Pillai, Elizabeth O. Hexner, Mark R. Philips, Wei Tong
Summary: RAB27B controls the palmitoylation and trafficking of NRAS, and its expression is associated with poor prognosis in AMLs. RAB27B depletion inhibits the growth of CBL-deficient or NRAS-mutant cell lines.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Editorial Material
Oncology
Xiuning Le, Monique B. Nilsson, Jacqulyne P. Robichaux, John V. Heymach
Summary: The ARTEMIS study showed that combining the VEGF inhibitor bevacizumab with the EGFR inhibitor erlotinib can significantly improve progression-free survival in patients with EGFR mutant non-small-cell lung cancer, especially in those with brain metastases and the EGFR L858R mutation. This suggests the potential benefits of tailored use of VEGF/EGFR combinations in this patient population.
Article
Oncology
Kun-Han Lee, Wei-Shone Chen, Jeng-Kai Jiang, Shung-Haur Yang, Huann-Sheng Wang, Shih-Ching Chang, Yuan-Tzu Lan, Chun-Chi Lin, Hung-Hsin Lin, Sheng-Chieh Huang, Hou-Hsuan Cheng, Yee Chao, Hao-Wei Teng
Summary: Metastatic middle/low rectal cancer shows lower efficacy in anti-EGFR treatment compared to left-sided colon cancer, both in terms of progression-free survival, overall survival, and overall response rates for both first-line and non-first-line treatment. TCGA analysis reveals genetic heterogeneity in rectal tumors, showing shared features with both left- and right-sided colon cancer.
BRITISH JOURNAL OF CANCER
(2021)
Article
Oncology
David J. Propper, Fangfei Gao, Mark P. Saunders, Debashis Sarker, John A. Hartley, Victoria J. Spanswick, Helen L. Lowe, Louise D. Hackett, Tony T. Ng, Paul R. Barber, Gregory E. Weitsman, Sarah Pearce, Laura White, Andre Lopes, Sharon Forsyth, Daniel Hochhauser
Summary: This study examined the toxicity and efficacy of high-dose pulsed AZD8931 combined with chemotherapy in metastatic colorectal cancer. Results showed acceptable toxicity and some patients had good response to the treatment. Furthermore, a reduction in circulating HER2/3 dimer was observed after treatment.
BRITISH JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Liangkun You, Xinnan Zheng, Danchen Deng, Hongming Pan, Weidong Han
Summary: Patients with EGFR L858R mutation treated with anti-angiogenic therapy had a significantly prolonged overall survival compared to those who had not received the treatment. The therapy also showed potential to improve overall survival in patients with liver and brain metastases.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Mari Tone, Kota Iwahori, Takayuki Shiroyama, Shinji Futami, Yujiro Naito, Kiyoharu Fukushima, Kotaro Miyake, Shohei Koyama, Haruhiko Hirata, Izumi Nagatomo, Hisashi Wada, Yoshito Takeda, Atsushi Kumanogoh
Summary: Minocycline administration in NSCLC patients treated with first-line EGFR-TKIs was found to correlate with longer PFS and OS, independent of skin rash. This retrospective analysis suggests that minocycline may have a positive impact on the treatment outcomes of EGFR-mutant NSCLC patients.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Gad Rennert, Maya Gottfried, Hedy S. Rennert, Flavio Lejbkowicz, Meira Frank, Ilana Cohen, Shiri Kelt, Abed Agbarya, Elizabeta Dudnik, Julia Dudnik, Rivka Katznelson, Moshe Mishali, Natalie Maimon Rabinovich, Hovav Nechushtan, Amir Onn, Shoshana Keren Rosenberg, Mariana Wollner, Alona Zer, Jair Bar, Naomi Gronich
Summary: The study showed that TKIs provided to EGFR mutated advanced NSCLC patients resulted in significant survival benefits for at least five years, but treating non-EGFR mutated NSCLC patients with TKIs seemed detrimental. Squamous histology, smoking, male sex, and Arab ethnicity were associated with higher NSCLC mortality hazard.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Kowit Hengphasatporn, Thitinan Aiebchun, Panupong Mahalapbutr, Atima Auepattanapong, Onnicha Khaikate, Kiattawee Choowongkomon, Chutima Kuhakarn, Jatuporn Meesin, Yasuteru Shigeta, Thanyada Rungrotmongkol
Summary: This study investigated the kinase inhibitory activities of a series of sulfonylated indeno-[1,2-c]-quinolines (SIQs) against EGFR-TK. Among the 23 SIQ derivatives studied, eight compounds showed enhanced EGFR-TK inhibitory activity compared to erlotinib. In cell-based assays, these eight compounds exhibited more significant cytotoxicity against A431 cells with higher EGFR expression. Overall, the potent SIQ compounds obtained in this work could be further optimized for developing novel anticancer drug candidates targeting EGFR-TK.
Review
Biochemistry & Molecular Biology
Marika Franczak, Isabel Toenshoff, Gerrit Jansen, Ryszard T. Smolenski, Elisa Giovannetti, Godefridus J. Peters
Summary: Mitochondria are crucial for cancer cells as they play a significant role in their energy requirements and chemoresistance. Differences in energy metabolism, such as higher NAD(+) levels, the Warburg effect, and increased one-carbon metabolism, have been identified between cancer and normal cells. Targeting these metabolic pathways could be a promising approach for developing new anticancer drugs. Combining novel drugs with conventional agents may provide effective treatments for cancer.
CURRENT MEDICINAL CHEMISTRY
(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)
Article
Oncology
Alessandro Gregori, Cecilia Bergonzini, Mjriam Capula, Giulia Mantini, Fatemeh Khojasteh-Leylakoohi, Annalisa Comandatore, Ghazaleh Khalili-Tanha, Alireza Khooei, Luca Morelli, Amir Avan, Erik H. Danen, Thomas Schmidt, Elisa Giovannetti
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and chemoresistant cancer, with a stiff stroma surrounding it playing a role in chemoresistance. High expression of the mechanical sensor ITGA2 correlated with a poor prognosis in PDAC patients, and increased matrix stiffness led to the expression of ITGA2 and chemoresistance to gemcitabine. ITGA2 could be a potential therapeutic target to overcome gemcitabine resistance.
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)
Review
Oncology
Mahrou Vahabi, Bilal Dehni, Ines Antomas, Elisa Giovannetti, Godefridus J. Peters
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited improvement in mortality rate despite extensive research and clinical trials. There is a need for comprehensive molecular characterization to identify biomarkers for early detection and evaluation of treatment response. MicroRNAs (miRNAs) show promise as stable biomarkers that can be detected in fixed tissues and biofluids, and their deregulation plays a role in the oncogenesis and metastasis of PDAC. Several oncomiRs and TsmiRs have been identified that contribute to chemoresistance in PDAC, and miRNA-based therapy approaches have shown success in vivo. Integrating miRNAs in PDAC treatment holds potential for personalized medicine.
CANCER AND METASTASIS REVIEWS
(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
Chemistry, Medicinal
Daniela Carbone, Camilla Pecoraro, Giovanna Panzeca, Geng Xu, Margot S. F. Roeten, Stella Cascioferro, Elisa Giovannetti, Patrizia Diana, Barbara Parrino
Summary: A series of new nortopsentin analogs were successfully synthesized by replacing the central imidazole ring with a 1,3,4-oxadiazole or 1,3,4-thiadiazole moiety. The antiproliferative activity of these derivatives was evaluated against pancreatic cancer cell lines, showing significant reduction in cell migration. Cell cycle analysis indicated cell cycle arrest and inhibition of CDK1 activity, a crucial regulator of cell cycle progression and cancer cell proliferation.
Article
Oncology
Maryam Alaei, Seyedeh Elnaz Nazari, Ghazaleh Pourali, AliReza Asadnia, Mehrdad Moetamani-Ahmadi, Hamid Fiuji, Hamid Tanzadehpanah, Fereshteh Asgharzadeh, Fatemeh Babaei, Fatemeh Khojasteh-Leylakoohi, Ibrahim Saeed Gataa, Mohammad Ali Kiani, Gordon A. Ferns, Alfred King-yin Lam, Seyed Mahdi Hassanian, Majid Khazaei, Elisa Giovannetti, Amir Avan
Summary: In this study, the potential of targeting the enzyme cytochrome P450 (CYP450) using lopinavir/ritonavir in colorectal cancer (CRC) was explored. Experimental methods were employed to assess the effects of lopinavir/ritonavir on CRC, and it was found that inhibiting CYP450 reduced cell proliferation, induced cell death, and suppressed cell migration. Lopinavir/ritonavir also inhibited tumor growth and fibrosis. These findings suggest that targeting CYP450 with lopinavir/ritonavir has therapeutic potential in CRC and further research in this area is needed.
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.
Article
Medicine, General & Internal
Antonio Doronzo, Letizia Porcelli, Donatello Marziliano, Gianfranco Inglese, Antonella Argentiero, Amalia Azzariti, Antonio Giovanni Solimando
Summary: This study analyzed the gene expression differences in pancreatic ductal adenocarcinoma (PDAC) patients based on their alcohol consumption history. The findings revealed that alcohol consumption is associated with the activation of the TGF beta pathway, which is implicated in cancer development and tumor progression. Inhibition of this pathway may serve as a novel therapeutic target for PDAC patients with a history of alcohol consumption.
MEDICINA-LITHUANIA
(2023)
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)