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
Oncology
Said A. Khelwatty, Soozana Puvanenthiran, Sharadah Essapen, Izhar Bagwan, Alan M. Seddon, Helmout Modjtahedi
Summary: The study revealed that high levels of HER2 expression were found in CRC patients treated with cetuximab, which was associated with shorter progression free survival. The results support the emergence of HER2 as a therapeutic target in mCRC patients.
Article
Gastroenterology & Hepatology
Laura Rosa Mangiapane, Annalisa Nicotra, Alice Turdo, Miriam Gaggianesi, Paola Bianca, Simone Di Franco, Davide Stefano Sardina, Veronica Veschi, Michele Signore, Sven Beyes, Luca Fagnocchi, Micol Eleonora Fiori, Maria Rita Bongiorno, Melania Lo Iacono, Irene Pillitteri, Gloria Ganduscio, Gaspare Gulotta, Jan Paul Medema, Alessio Zippo, Matilde Todaro, Ruggero De Maria, Giorgio Stassi
Summary: In colorectal cancer stem cells, high HER2 expression levels are associated with activation of the PI3K/AKT pathway. The targeting of HER2 in combination with PI3K and MEK inhibitors induces CR-CSC death and regression of tumor xenografts, including those with specific mutations. Triple targeting of PI3K, HER2, and MEK is necessary to overcome resistance to anti-EGFR therapies.
Article
Oncology
Stefano Mariani, Marco Puzzoni, Riccardo Giampieri, Pina Ziranu, Valeria Pusceddu, Clelia Donisi, Mara Persano, Giovanna Pinna, Erika Cimbro, Alissa Parrino, Dario Spanu, Andrea Pretta, Eleonora Lai, Nicole Liscia, Alessio Lupi, Enrica Giglio, Grazia Palomba, Milena Casula, Marina Pisano, Giuseppe Palmieri, Mario Scartozzi
Summary: This study investigated the efficacy of liquid biopsy-driven cetuximab rechallenge in a selected population of CRC patients with RAS and BRAF WT. The results showed that liquid biopsy-driven cetuximab rechallenge was effective and consistent with previous phase II studies. In addition to molecular selection, a longer anti-EGFR free interval was confirmed as an important predictor for this therapeutic option.
FRONTIERS IN ONCOLOGY
(2022)
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
Elaine S. Tan, Wenyi Fan, Todd C. Knepper, Michael J. Schell, Ibrahim H. Sahin, Jason B. Fleming, Hao Xie
Summary: This study found that PIK3CA mutations are poor prognostic factors in colorectal cancer and the meta-analysis confirmed that PIK3CA mutations predict a reduced response to anti-EGFR therapy in patients with metastatic colorectal cancer.
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)
Editorial Material
Gastroenterology & Hepatology
Sen Lu, Cheng-You Jia, Jian-She Yang
Summary: Colorectal cancer (CRC) ranks second among malignant tumors globally in 2020 due to its high incidence and mortality rates. Treatment strategies now rely heavily on the molecular characteristics of CRC. While classical theories propose two models for CRC origin, adenoma progression and serrated polyp transformation, the molecular mechanism of CRC development is highly complex. This article introduces another possible pathway, particularly from laterally spreading tumors (LST), with important molecular characteristics, which could lead to the development of a novel targeted therapy strategy.
WORLD JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Oncology
Michel Ducreux, Josep Tabernero, Axel Grothey, Dirk Arnold, Peter J. O'Dwyer, Frank Gilberg, Alexander Abbas, Meghna Das Thakur, Hen Prizant, Natsumi Irahara, Anila Tahiri, Hans -Joachim Schmoll, Eric Van Cutsem, Aimery de Gramont
Summary: This study aimed to explore the feasibility of biomarker-driven maintenance therapy in patients with metastatic colorectal cancer. The findings suggest that vemurafenib plus cetuximab plus 5-FU/LV may be further investigated as first-line maintenance treatment for BRAF(mut) mCRC. However, cobimetinib plus atezolizumab had an unfavorable benefit:risk ratio in HER2-/MSS/BRAF(wt) mCRC.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Pharmacology & Pharmacy
Ye Li, Yuncang Yuan, Fan Zhang, Aizhen Guo, Fuao Cao, Mengmeng Song, Yating Fu, Xiaowen Xu, Hao Shen, Shangyong Zheng, Yamin Pan, Wenjun Chang
Summary: Our study found that frequent resistance to SHP2 inhibitors exists in colorectal carcinoma cells, even in those without RAS mutations. Rapid adaptive reactivation of the AKT pathway in response to SHP2 inhibition may contribute to this resistance, driven by the reactivation of RTKs or released p-FAK. Co-inhibition of FAK abrogated the feedback reactivation of AKT in response to SHP2 inhibition, leading to sustained AKT pathway suppression and improved antitumor efficacy.
FRONTIERS IN PHARMACOLOGY
(2021)
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
Jonathan M. Loree, Anthony Dowers, Dongsheng Tu, Derek J. Jonker, Daniel L. Edelstein, Hannah Quinn, Frank Holtrup, Timothy Price, John R. Zalcberg, Malcolm J. Moore, Christos S. Karapetis, Chris J. O'Callaghan, Paul Waring, Hagen F. Kennecke, Stanley R. Hamilton, Scott Kopetz
Summary: The study aimed to establish the efficacy of single-agent cetuximab in optimally selected patients using BEAMing analysis. Results showed that cetuximab improved overall survival and progression-free survival in RAS/BRAF wild-type patients, but had no significant effect on patients with KRAS, NRAS, or BRAF mutations. Subclonal RAS/BRAF alterations were found to be rare and of uncertain significance.
CLINICAL CANCER RESEARCH
(2021)
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
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.
Article
Biochemistry & Molecular Biology
Catarina Silveira, Ana Carla Sousa, Patricia Corredeira, Marta Martins, Ana Rita Sousa, Arnaud Da Cruz Paula, Pier Selenica, David N. Brown, Mahdi Golkaram, Shannon Kaplan, Shile Zhang, Li Liu, Britta Weigelt, Jorge S. Reis-Filho, Luis Costa, Maria Carmo-Fonseca
Summary: Analysis of cell-free circulating tumor DNA obtained by liquid biopsy can provide clinically actionable information for treatment response in breast cancer patients, especially when conventional tissue biopsy is inaccessible. This study identified a mutation in the PIK3CA gene and amplification of the CCND1 gene in circulating cell-free DNA, which disappeared after treatment.
Review
Medicine, General & Internal
Cecilia Melo-Alvim, Maria Eduarda Neves, Jorge Leitao Santos, Andre N. Abrunhosa-Branquinho, Tiago Barroso, Luis Costa, Leonor Ribeiro
Summary: Oral squamous cell carcinoma, the most common malignant epithelial neoplasm in the oral cavity, often cannot be treated with surgical resection due to recurrent or metastatic characteristics. Non-surgical therapeutic options such as radiotherapy, chemotherapy, molecular targeted agents, and immunotherapy are important alternatives. The effectiveness and side effects of these treatments should be carefully considered in a multidisciplinary approach.
Article
Biochemistry & Molecular Biology
Tito Palmela Leitao, Patricia Corredeira, Sandra Kucharczak, Margarida Rodrigues, Paulina Piairo, Carolina Rodrigues, Patricia Alves, Ana Martins Cavaco, Miguel Miranda, Marilia Antunes, Joao Ferreira, Jose Palma Reis, Tome Lopes, Lorena Dieguez, Luis Costa
Summary: Renal cell carcinoma (RCC) often presents as metastatic disease. Research on circulating tumor cells (CTCs) and liquid biopsies is improving understanding of RCC biology and metastasis formation. This study aimed to clinically validate the effectiveness of RUBYchip (TM), a microfluidic label-free CTC detection platform, in RCC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Daniela Cochicho, Alexandra Nunes, Daniel Sobral, Joao P. Gomes, Susana Esteves, Joana Mendonca, Luis Vieira, Luis Martins, Mario Cunha, Pedro Montalvao, Miguel Magalhaes, Rui M. Gil da Costa, Ana Maria Felix
Summary: This study analyzed HPV16 variants in HNSCC patients and found no significant associations with clinical-pathological characteristics or patient survival.
Review
Oncology
Miguel Esperanca-Martins, Diogo Roque, Tiago Barroso, Andre Abrunhosa-Branquinho, Diogo Belo, Nuno Simas, Luis Costa
Summary: The prevalence of metastatic spine disease is increasing and requires a multidisciplinary approach for optimal clinical outcomes. We reviewed recent data and proposed an updated algorithmic approach to personalized management. A flowchart-based approach provides evidence-based decision-making in a context of uncertainty and urgency.
Article
Biochemistry & Molecular Biology
Ana Peixoto, Luis Cirnes, Ana Luisa Carvalho, Maria Joao Andrade, Maria Jose Brito, Paula Borralho, Pedro M. Borralho, Ana Sofia Carneiro, Lisandra Castro, Lurdes Correia, Maria Rita Dionisio, Carlos Faria, Paulo Figueiredo, Ana Gomes, Joana Paixao, Manuela Pinheiro, Hugo Prazeres, Joana Ribeiro, Natalia Salgueiro, Fernando C. Schmitt, Fatima Silva, Ana Rita Silvestre, Ana Carla Sousa, Joana Almeida-Tavares, Manuel R. Teixeira, Saudade Andre, Jose Carlos Machado
Summary: The U-PIK project aimed to validate and implement the PIK3CA mutation testing in multiple Portuguese centers, and the testing results showed high concordance rates between the method used by each tester center and NGS, demonstrating the importance of this test in clinical practice for ER+/HER2-BC patients eligible for PI3K alpha inhibitor treatment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Tiago Barroso, Cecilia Melo-Alvim, Leonor Abreu Ribeiro, Sandra Casimiro, Luis Costa
Summary: Precision oncology aims to treat cancer while preserving the integrity of healthy cells and tissues. Classical chemotherapy and radiotherapy can still induce apoptosis in cancer cells, but inhibitors of apoptosis proteins may prevent apoptosis. Recently, inhibitors of these proteins, such as xevinapant, have been developed to enhance the cytotoxic effects of traditional treatments, showing effectiveness in clinical trials. This represents a synergistic approach between classic cytotoxic treatments and new targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Roger Feakins, Paula Borralho Nunes, Ann Driessen, Ilyssa O. Gordon, Nina Zidar, Pamela Baldin, Britt Christensen, Silvio Danese, Naoimh Herlihy, Marietta Iacucci, Maurice B. Loughrey, Fernando Magro, Aart Mookhoek, Magali Svrcek, Francesca Rosini
Summary: Histological assessment is important in the management and study of inflammatory bowel disease (IBD), but definitions and recognition of abnormal histological features are often inconsistent. The European Crohn's and Colitis Organisation (ECCO) formed an expert panel to explore and improve the quality of diagnosis by producing a series of consensus statements on histological features in IBD.
JOURNAL OF CROHNS & COLITIS
(2023)
Review
Oncology
Miguel Esperanca-Martins, Cecilia Melo-Alvim, Sara Damaso, Raquel Lopes-Bras, Tania Peniche, Goncalo Nogueira-Costa, Catarina Abreu, Helena Luna Pais, Rita Teixeira de Sousa, Sofia Torres, Lina Marcela Gallego-Paez, Marta Martins, Leonor Ribeiro, Luis Costa
Summary: Breast sarcomas, phyllodes tumors, and desmoid tumors are rare and poorly characterized entities. This article aims to provide new data for researchers and a decision-making tool for clinicians when treating patients with these tumors.
Review
Oncology
Ines Gomes, Catarina Abreu, Luis Costa, Sandra Casimiro
Summary: This review provides an overview of the latest research on the efficacy and resistance of CDK4/6 inhibitors, highlighting the challenges brought by basic treatment for breast cancer and proposing possible treatment strategies.
Article
Cell Biology
Lisa Goncalves, Duarte Goncalves, Teresa Esteban-Casanelles, Tiago Barroso, Ines Soares de Pinho, Raquel Lopes-Bras, Miguel Esperanca-Martins, Vanessa Patel, Sofia Torres, Rita Teixeira de Sousa, Andre Mansinho, Luis Costa
Summary: Although the impact of circadian timing on immunotherapy has not been implemented in clinical practice yet, chronoimmunotherapy shows potential as circadian oscillations are observed in immune cell numbers and the expression of immunotherapy targets. Retrospective studies suggest that morning infusions may lead to higher effectiveness of immune checkpoint inhibitors in melanoma, non-small cell lung cancer, and kidney cancer.
Article
Oncology
Ines Brandao Rego, Sara Coelho, Patricia Miguel Semedo, Joana Cavaco-Silva, Laetitia Teixeira, Susana Sousa, Joana Reis, Rui Dinis, Fernando Schmitt, Noemia Afonso, Jose Luis Fougo, Francisco Pavao, Ricardo Baptista Leite, Luis Costa
Summary: This study aims to describe the compliance with EUSOMA indicators in breast cancer management in different hospital settings in Portugal. Although most indicators meet EUSOMA standards, there are differences among institutions, especially in diagnosis and disease stages.
Article
Cell Biology
Mounir El Mai, Malia Bird, Asma Allouche, Seniye Targen, Naz Serifoglu, Bruno Lopes-Bastos, Jean-Marie Guigonis, Da Kang, Thierry Pourcher, Jia-Xing Yue, Miguel Godinho Ferreira
Summary: This study demonstrates that gut-specific telomerase expression is sufficient to rescue aging phenotypes and extend the lifespan of telomerase-deficient zebrafish, as well as ameliorate signs of aging in wild-type animals. The specific telomerase expression in the gut prevents telomere shortening, rescues premature aging, and has systemic beneficial impacts on distant organs such as the reproductive and hematopoietic systems.