Article
Biochemistry & Molecular Biology
Joris van de Haar, Xuhui Ma, Salo N. Ooft, Pim W. van der Helm, Louisa R. Hoes, Sara Mainardi, David J. Pinato, Kristi Sun, Lisa Salvatore, Giampaolo Tortora, Ina Valeria Zurlo, Silvana Leo, Riccardo Giampieri, Rossana Berardi, Fabio Gelsomino, Valeria Merz, Federica Mazzuca, Lorenzo Antonuzzo, Gerardo Rosati, Chara Stavraka, Paul Ross, Maria Grazia Rodriquenz, Michele Pavarana, Carlo Messina, Timothy Iveson, Federica Zoratto, Anne Thomas, Elisabetta Fenocchio, Margherita Ratti, Ilaria Depetris, Massimiliano Cergnul, Cristina Morelli, Michela Libertini, Alessandro Parisi, Michele De Tursi, Nicoletta Zanaletti, Ornella Garrone, Janet Graham, Raffaella Longarini, Stefania Maria Gobba, Angelica Petrillo, Emiliano Tamburini, Nicla La Verde, Fausto Petrelli, Vincenzo Ricci, Lodewyk F. A. Wessels, Michele Ghidini, Alessio Cortellini, Emile E. Voest, Nicola Valeri
Summary: Genomic analysis identified KRAS(G12) mutations as potential biomarkers of resistance to trifluridine/tipiracil treatment in metastatic colorectal cancer. Real-world data and phase 3 clinical trial data confirmed the significant association between KRAS(G12) mutations and reduced overall survival. These findings provide important implications for precision medicine in approximately 28% of patients with metastatic colorectal cancer.
Review
Biochemistry & Molecular Biology
Lulin Ma, Wenjing Zhao, Shiqian Huang, Feng Xu, Yafeng Wang, Daling Deng, Tianhao Zhang, Shaofang Shu, Xiangdong Chen
Summary: Pain, an important problem in medicine and public health, has significant research significance. Opioids are currently the main drugs used to relieve pain, but their use is limited due to obvious side effects. Therefore, there is an urgent need to develop new drugs for pain relief. Multiple studies have shown that the IGF/IGF-1R pathway plays a crucial role in the occurrence and development of pain. This review summarizes and discusses the therapeutic potential of the IGF/IGF-1R signal pathway for pain. It also highlights the regulation of pain by IGF/IGF-1R through actions on neuronal excitability, neuroinflammation, glial cells, apoptosis, and more. However, further research is still needed to fully understand the mechanisms of pain occurrence and development. In conclusion, while more in-depth studies are required, these findings suggest that the IGF/IGF-1R signal pathway holds promise as a therapeutic target for pain.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Oncology
Christopher J. M. Williams, Jenny F. Seligmann, Faye Elliott, Michael Shires, Susan D. Richman, Sarah Brown, Liping Zhang, Shalini Singh, Judith Pugh, Xiao-Meng Xu, Andrea Muranyi, Christoph Guetter, Auranuch Lorsakul, Uday Kurkure, Zuo Zhao, Jim Martin, Xingwei Wang, Kien Nguyen, Wen-Wei Liu, Dongyao Yan, Nicholas P. West, Jennifer H. Barrett, Michael Barnes, Isaac Bai, Matthew T. Seymour, Philip Quirke, Kandavel Shanmugam
Summary: The study demonstrated that high tumor mRNA levels of the EGFR ligands AREG and EREG were associated with a significant progression-free survival benefit from the anti-EGFR agent panitumumab in metastatic colorectal cancer patients. Additionally, the RECIST response rate was significantly improved in patients with high ligand expression, highlighting the potential of AREG/EREG IHC as a predictive tool for treatment response in routine practice.
CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Maria Dobre, Vlad Herlea, Catalina Vladut, Mihai Ciocirlan, Vasile Daniel Balaban, Gabriel Constantinescu, Mircea Diculescu, Elena Milanesi
Summary: The study identified a panel of downregulated miRNAs in PDAC tissue, which could serve as potential therapeutic targets for the development of new miRNA-based therapies for PDAC.
Review
Pharmacology & Pharmacy
Zaina T. Al-Salama
Summary: Encorafenib in combination with cetuximab has shown significantly longer overall survival, higher response rate, and better tolerability in patients with mCRC and a BRAF V600E mutation who have had prior therapy.
Article
Oncology
Jingyuan Wang, Yi Xiao, Fotios Loupakis, Sebastian Stintzing, Yan Yang, Hiroyuki Arai, Francesca Battaglin, Natsuko Kawanishi, Priya Jayachandran, Shivani Soni, Wu Zhang, Christoph Mancao, Chiara Cremolini, Tianshu Liu, Volker Heinemann, Alfredo Falcone, Lin Shen, Joshua Millstein, Heinz-Josef Lenz
Summary: This study found that genetic polymorphisms in the cGAS-STING pathway may predict the efficacy of cetuximab-based treatment in patients with metastatic colorectal cancer. This has important implications for the development of personalized treatment strategies.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Giovanni Randon, Rona Yaeger, Jaclyn F. Hechtman, Paolo Manca, Giovanni Fuca, Henry Walch, Jeeyun Lee, Elena Elez, Jenny Seligmann, Benedetta Mussolin, Filippo Pagani, Marco Maria Germani, Margherita Ambrosini, Daniele Rossini, Margherita Ratti, Francesc Salva, Susan D. Richman, Henry Wood, Gouri Nanjangud, Annunziata Gloghini, Massimo Milione, Alberto Bardelli, Filippo de Braud, Federica Morano, Chiara Cremolini, Filippo Pietrantonio
Summary: EGFR amplification is significantly associated with left primary tumor sidedness and RAS/BRAF wild-type status. EGFR-amplified tumors are usually MSS and HER2 nonamplified, with a higher median fraction of genome altered. Patients with EGFR amplification tend to have longer overall survival and better outcomes when exposed to anti-EGFR-based therapy.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Medicine, General & Internal
Gerald W. Prager, Julien Taieb, Marwan Fakih, Fortunato Ciardiello, Eric Van Cutsem, Elena Elez, Felipe M. Cruz, Lucjan Wyrwicz, Daniil Stroyakovskiy, Zsuzsanna Papai, Pierre-Guillaume Poureau, Gabor Liposits, Chiara Cremolini, Igor Bondarenko, Dominik P. Modest, Karim A. Benhadji, Nadia Amellal, Catherine Leger, Loick Vidot, Josep Tabernero
Summary: In this study, researchers found that treatment with trifluridine-tipiracil plus bevacizumab could prolong overall survival in patients with metastatic colorectal cancer compared to trifluridine-tipiracil alone.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Cell Biology
Stefano Cavalieri, Mara Serena Serafini, Andrea Carenzo, Silvana Canevari, Deborah Lenoci, Federico Pistore, Rosalba Miceli, Stefania Vecchio, Daris Ferrari, Cecilia Moro, Andrea Sponghini, Alessia Caldara, Maria Cossu Rocca, Simona Secondino, Gabriella Moretti, Nerina Denaro, Francesco Caponigro, Emanuela Vaccher, Gaetana Rinaldi, Francesco Ferrau, Paolo Bossi, Lisa Licitra, Loris De Cecco
Summary: This study evaluates the prognostic significance of a four-gene inflammatory signature in recurrent/metastatic head and neck squamous cell carcinoma patients treated with the EGFR inhibitor cetuximab plus chemotherapy. The results show that patients with high values of the signature have significantly better progression-free survival and overall survival compared to those with intermediate and low values. The signature also correlates with treatment response.
Article
Oncology
Jiawei Zhou, Quefeng Li, Yanguang Cao
Summary: The response of metastatic lesions varies across different anatomic sites and therapies. High interlesion heterogeneity is associated with shorter survival, highlighting the potential benefits of targeted therapies in reducing heterogeneity and improving efficacy. Favorable responses in liver metastases are linked to extended overall survival, while lesions in other organs show less favorable outcomes.
Article
Biochemistry & Molecular Biology
Hiroyuki Arai, Andrew Elliott, Joshua Millstein, Joanne Xiu, Fang-Shu Ou, Federico Innocenti, Jingyuan Wang, Francesca Battaglin, Priya Jayachandran, Natsuko Kawanishi, Shivani Soni, Wu Zhang, Davendra Sohal, Richard M. Goldberg, Michael J. Hall, Aaron J. Scott, Mohd Khushman, Jimmy J. Hwang, Emil Lou, Benjamin A. Weinberg, Albert Craig Lockhart, Anthony Frank Shields, Jim P. Abraham, Daniel Magee, Phillip Stafford, Jian Zhang, Alan P. Venook, W. Michael Korn, Heinz-Josef Lenz
Summary: Loss-of-function alterations in NF1 gene activate RAS, a driver of colorectal cancer. NF1-mutant tumors frequently also have mutations in PIK3CA and PTEN genes. Low NF1 expression may be associated with poor prognosis, while high expression may enhance the efficacy of cetuximab compared to bevacizumab. Further investigation in clinical settings is needed to explore the potential of NF1 alteration as a novel biomarker for targeted therapy.
Article
Medicine, General & Internal
Kishan K. Patel, Stacey Stein, Jill Lacy, Mark O'Hara, Scott F. Huntington
Summary: The study found that doublet therapy for metastatic BRAF variant colorectal cancer may not be cost-effective. Cost-effectiveness requires consideration, especially when combining new therapies with non-cost-effective treatments.
Article
Oncology
Marcin Szemitko, Elzbieta Golubinska-Szemitko, Jerzy Sienko, Aleksander Falkowski, Ireneusz Wiernicki
Summary: The aim of this study was to investigate the efficacy of irinotecan-releasing beads in the treatment of metastatic colorectal cancer after prior cetuximab monotherapy. The study found no statistically significant difference in radiological response to treatment based on prior cetuximab therapy, but a significant correlation between low baseline CEA values and treatment response. Prior treatment with anti-EGFR antibodies did not significantly affect radiological response or post-treatment progression.
Article
Gastroenterology & Hepatology
Sophie L. Boos, Leon P. Loevenich, Sebastian Vosberg, Thomas Engleitner, Rupert Ollinger, Joerg Kumbrink, Matjaz Rokavec, Marlies Michl, Philipp A. Greif, Andreas Jung, Heiko Hermeking, Jens Neumann, Thomas Kirchner, Roland Rad, Peter Jung
Summary: The study found that metastatic colorectal cancer organoids exhibited transcriptomic changes rather than gene mutations during adaptation to combination chemotherapy. Introduction of KRAS(G12D) increased the resilience of drug-tolerant CRC organoids against combination therapy. AURKA inhibition helped restore apoptotic response in drug-tolerant CRC organoids.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elena Elez, Javier Ros, Jose Fernandez, Guillermo Villacampa, Ana Belen Moreno-Cardenas, Carlota Arenillas, Kinga Bernatowicz, Raquel Comas, Shanshan Li, David Philip Kodack, Roberta Fasani, Ariadna Garcia, Javier Gonzalo-Ruiz, Alejandro Piris-Gimenez, Paolo Nuciforo, Grainne Kerr, Rossana Intini, Aldo Montagna, Marco Maria Germani, Giovanni Randon, Ana Vivancos, Ron Smits, Diana Graus, Raquel Perez-Lopez, Chiara Cremolini, Sara Lonardi, Filippo Pietrantonio, Rodrigo Dienstmann, Josep Tabernero, Rodrigo A. Toledo
Summary: In colorectal cancer patients, inactivating mutations in the RNF43 gene are associated with patients' response rates and survival outcomes to anti-BRAF/EGFR therapy. This suggests that the status of the RNF43 gene may serve as a predictive biomarker for patients' clinical outcomes.