Review
Oncology
Davide Ciardiello, Giulia Martini, Vincenzo Famiglietti, Stefania Napolitano, Vincenzo De Falco, Teresa Troiani, Tiziana Pia Latiano, Javier Ros, Elena Elez Fernandez, Pietro Paolo Vitiello, Evaristo Maiello, Fortunato Ciardiello, Erika Martinelli
Summary: For patients with metastatic colorectal cancer (mCRC) who have progressed through first and second line treatments, the prognosis is poor and new therapeutic strategies are necessary. Emerging evidence suggests that retreatment with anti-EGFR monoclonal antibodies in the third line of therapy could lead to prolonged survival for patients who have previously benefitted from first-line therapy with anti-EGFR antibodies. The rationale behind this strategy is that after a break from anti-EGFR drugs, resistance in cancer cells may decline, making them sensitive to treatment with cetuximab and panitumumab.
Article
Oncology
Yoshitaka Saito, Kazuki Uchiyama, Yoh Takekuma, Yoshito Komatsu, Mitsuru Sugawara
Summary: A retrospective evaluation of mCRC patients receiving anti-EGFR monoclonal antibody treatment identified liver metastasis as an independent risk factor for skin toxicities and prophylactic administration of antibiotics as a preventive factor. The study suggests that preemptive antibiotic use can decrease the risk of skin toxicities during anti-EGFR treatment.
SUPPORTIVE CARE IN CANCER
(2023)
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
Oncology
Demetris Papamichael, Guilherme S. Lopes, Curt L. Olswold, Jean-Yves Douillard, Richard A. Adams, Timothy S. Maughan, Eric Van Cutsem, Alan P. Venook, Heinz-Josef Lenz, Volker Heinemann, Richard Kaplan, Carsten Bokemeyer, Benoist Chibaudel, Axel Grothey, Takayuki Yoshino, John Zalcberg, Aimery De Gramont, Qian Shi
Summary: The efficacy and safety of adding anti-EGFR agents to doublet chemotherapy in older patients were investigated. The results showed that adding anti-EGFR agents did not significantly improve progression-free survival and overall survival in older patients. In contrast, younger patients showed better efficacy and survival after the addition of anti-EGFR agents.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Multidisciplinary Sciences
Takayuki Yoshino, Maria Di Bartolomeo, Kanwal Raghav, Toshiki Masuishi, Fotios Loupakis, Hisato Kawakami, Kensei Yamaguchi, Tomohiro Nishina, Zev Wainberg, Elena Elez, Javier Rodriguez, Marwan Fakih, Fortunato Ciardiello, Kapil Saxena, Kojiro Kobayashi, Emarjola Bako, Yasuyuki Okuda, Gerold Meinhardt, Axel Grothey, Salvatore Siena
Summary: This article reports the final results of a multicenter, open-label, phase 2 trial assessing the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with HER2-expressing metastatic colorectal cancer (mCRC). The primary analysis showed an objective response rate (ORR) of 45.3% in HER2-positive patients, while no responses were observed in other HER2 statuses. The most common adverse events of T-DXd were decreased neutrophil count and anemia. These findings support further exploration of T-DXd in HER2-positive mCRC.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Paolo Manca, Salvatore Corallo, Adele Busico, Sara Lonardi, Francesca Corti, Carlotta Antoniotti, Letizia Procaccio, Matteo Clavarezza, Valeria Smiroldo, Gianluca Tomasello, Roberto Murialdo, Andrea Sartore-Bianchi, Patrizia Racca, Filippo Pagani, Giovanni Randon, Antonia Martinetti, Elisa Sottotetti, Federica Palermo, Federica Perrone, Elena Tamborini, Michele Prisciandaro, Alessandra Raimondi, Maria Di Bartolomeo, Federica Morano, Filippo Pietrantonio
Summary: Analysis of ctDNA in mCRC patients revealed that the presence of RAS or PIK3CA mutations in baseline ctDNA is associated with worse PFS and OS, which can help refine the selection of patients for upfront anti-EGFR strategies.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Jonathan M. Loree, Yucai Wang, Muddassir A. Syed, Alexey Sorokin, Oluwadara Coker, Joanne Xiu, Benjamin A. Weinberg, Ari M. Vanderwalde, Anteneh Tesfaye, Victoria M. Raymond, Benjamin Miron, Gabi Tarcic, Ori Zelichov, Russell R. Broaddus, Patrick Kwok Shing Ng, Kang Jin Jeong, Yiu Huen Tsang, Gordon B. Mills, Michael J. Overman, Axel Grothey, John L. Marshall, Scott Kopetz
Summary: The study identified a high prevalence of atypical RAS mutations in colorectal cancer patients, which were associated with poor prognosis. Activating atypical variants were the most common in clinical cohorts, providing the best evidence to guide treatment.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
James T. Topham, Chris J. O'Callaghan, Harriet Feilotter, Hagen F. Kennecke, Young S. Lee, Weimin Li, Kimberly C. Banks, Katie Quinn, Daniel J. Renouf, Derek J. Jonker, Dongsheng Tu, Eric X. Chen, Jonathan M. Loree
Summary: This study aimed to explore the acquired resistance mechanisms in metastatic colorectal cancer patients after anti-epidermal growth factor receptor (EGFR) antibody treatment. The results indicated that multiple genes experienced increased mutation frequency, concurrent alterations, and copy gains in patients following anti-EGFR therapy. Furthermore, gene fusions were found to be associated with prior anti-EGFR therapy. The study also highlighted the prevalence of polyclonal resistance in patients with prior anti-EGFR treatment. This research provides valuable insights into the acquired resistance mechanisms of anti-EGFR therapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Wen Zhang, Xiaohong Han, Lin Yang, Yuanyuan Song, Liangzhi Xie, Wenlin Gai, Yan Wang, Yuankai Shi
Summary: SCT200 demonstrated favorable safety, pharmacokinetic profile, and preliminary efficacy in patients with wild-type KRAS/NRAS/BRAF metastatic colorectal cancer, with low toxicity.
Article
Medicine, General & Internal
Rona Yaeger, Jared Weiss, Meredith S. Pelster, Alexander Spira, Minal Barve, Sai-Hong Ou, Ticiana A. Leal, Tanios S. Bekaii-Saab, Cloud P. Paweletz, Grace A. Heavey, James G. Christensen, Karen Velastegui, Thian Kheoh, Hirak Der-Torossian, Samuel J. Klempner
Summary: In this study, the researchers investigated the clinical efficacy of adagrasib in combination with cetuximab for heavily pretreated patients with metastatic colorectal cancer harboring mutant KRAS G12C. The results showed that the overall response rate was 19% in the adagrasib monotherapy group, with a median progression-free survival of 5.6 months, and 46% in the combination therapy group, with a median progression-free survival of 6.9 months. Both groups experienced reversible adverse events.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Engineering, Biomedical
Minji Ahn, Taebum Lee, Kyoung Sub Kim, Sanghee Lee, Kun Na
Summary: A novel platform combining antibody-mediated immunotherapy and photodynamic therapy has been developed to improve the efficacy of antibody-drug conjugates. The platform demonstrates remarkable anticancer effects by specifically targeting KRAS-mutated cancer cells and activating the immune system through a synergistic approach.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Oncology
Guillermo Valenzuela, Mauricio Burotto, Katherine Marcelain, Jaime Gonzalez-Montero
Summary: Colorectal cancer is a leading cause of death globally, with high molecular heterogeneity. Though targeted therapy for CRC has improved with the identification of mutations, there is still uncertainty in its effectiveness. The recent development of liquid biopsy may become a new standard in targeted CRC therapy decision-making.
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
(2022)
Article
Oncology
Josep Tabernero, Eric Van Cutsem, Elena Garralda, David Tai, Filippo De Braud, Ravit Geva, Mark T. J. van Bussel, Katia Fiorella Dotti, Elena Elez, Maria J. de Miguel, Kevin Litwiler, Danielle Murphy, Michelle Edwards, Van Karlyle Morris
Summary: This study evaluated the maximum tolerated dose of WNT974 in combination with encorafenib and cetuximab in patients with BRAF (V600E)-mutant metastatic colorectal cancer. The results showed a high incidence of adverse events and no evidence of improved anti-tumor activity, leading to study discontinuation.
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.
Article
Oncology
Benny Vittrup Jensen, Jakob Schou, Mette Yilmaz, Helle H. Johannesen, Kristin Skougaard, Dorte Linnemann, Estrid Hogdall, Finn O. Larsen, Julia S. Johansen, Per Pfeiffer, Dorte L. Nielsen
Summary: This study investigated the use of cetuximab and irinotecan in third-line treatment for mCRC patients, regardless of RAS or BRAF mutation status, and achieved certain efficacy. Shortening the treatment time while maintaining good treatment outcomes.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Cell Biology
Esther Conde, Alejandra Caminoa, Carolina Dominguez, Antonio Calles, Stefan Walter, Barbara Angulo, Elena Sanchez, Marta Alonso, Luis Jimenez, Luis Madrigal, Florentino Hernando, Julian Sanz-Ortega, Beatriz Jimenez, Pilar Garrido, Luis Paz-Ares, Javier de Castro, Susana Hernandez, Fernando Lopez-Rios
Review
Oncology
F. Losa, L. Iglesias, M. Pane, J. Sanz, B. Nieto, V. Fuste, L. de la Cruz-Merino, A. Concha, C. Balana, X. Matias-Guiu
CLINICAL & TRANSLATIONAL ONCOLOGY
(2018)
Article
Gastroenterology & Hepatology
Annalisa Addante, Cesareo Roncero, Laura Almale, Nerea Lazcanoiturburu, Maria Garcia-Alvaro, Margarita Fernandez, Julian Sanz, Seddik Hammad, Zeribe C. Nwosu, Se-Jin Lee, Isabel Fabregat, Steven Dooley, Peter ten Dijke, Blanca Herrera, Aranzazu Sanchez
LIVER INTERNATIONAL
(2018)
Letter
Oncology
S. Cabezas-Camarero, F. Puebla, A. I. Subhi-Issa, J. Sanz-Ortega, Pedro Perez-Segura
Article
Cell & Tissue Engineering
Laura Almale, Maria Garcia-Alvaro, Adoracion Martinez-Palacian, Maria Garcia-Bravo, Nerea Lazcanoiturburu, Annalisa Addante, Cesareo Roncero, Julian Sanz, Maria de la O Lopez, Paloma Bragado, Wolfgang Mikulits, Valentina M. Factor, Snorri S. Thorgeirsson, J. Ignacio Casal, Jose-Carlos Segovia, Eduardo Rial, Isabel Fabregat, Blanca Herrera, Aranzazu Sanchez
Article
Oncology
Esther Conde, Susana Hernandez, Rebeca Martinez, Barbara Angulo, Javier De Castro, Ana Collazo-Lorduy, Beatriz Jimenez, Alfonso Muriel, Jose Luis Mate, Teresa Moran, Ignacio Aranda, Bartomeu Massuti, Federico Rojo, Manuel Domine, Irene Sansano, Felip Garcia, Enriqueta Felip, Nuria Mancheno, Oscar Juan, Julian Sanz, Jose Luis Gonzalez-Larriba, Lidia Atienza-Cuevas, Esperanza Arriola-Arellano, Ihab Abdulkader, Jorge Garcia-Gonzalez, Carmen Camacho, Delvys Rodriguez-Abreu, Cristina Teixido, Noemi Reguart, Ana Gonzalez-Pineiro, Martin Lazaro-Quintela, Maria Dolores Lozano, Alfonso Gurpide, Javier Gomez-Roman, Marta Lopez-Brea, Lara Pijuan, Marta Salido, Edurne Arriola, Amparo Company, Amelia Insa, Isabel Esteban-Rodriguez, Monica Saiz, Eider Azkona, Ramiro Alvarez, Angel Artal, Maria Luz Plaza, David Aguiar, Ana Belen Enguita, Amparo Benito, Luis Paz-Ares, Pilar Garrido, Fernando Lopez-Rios
JOURNAL OF THORACIC ONCOLOGY
(2019)
Article
Multidisciplinary Sciences
Victor Lorca, Daniel Rueda, Lorena Martin-Morales, Maria Jesus Fernandez-Acenero, Judith Grolleman, Carmen Poves, Patricia Llovet, Sandra Tapial, Vanesa Garcia-Barberan, Julian Sanz, Pedro Perez-Segura, Richarda M. de Voer, Eduardo Diaz-Rubio, Miguel de la Hoya, Trinidad Caldes, Pilar Garre
SCIENTIFIC REPORTS
(2019)
Article
Oncology
P. Garrido, E. Conde, J. de Castro, J. J. Gomez-Roman, E. Felip, L. Pijuan, D. Isla, J. Sanz, L. Paz-Ares, F. Lopez-Rios
CLINICAL & TRANSLATIONAL ONCOLOGY
(2020)
Article
Oncology
Nerea Lazcanoiturburu, Juan Garcia-Saez, Carlos Gonzalez-Corralejo, Cesareo Roncero, Julian Sanz, Carlos Martin-Rodriguez, M. Pilar Valdecantos, Adoracion Martinez-Palacian, Laura Almale, Paloma Bragado, Silvia Calero-Perez, Almudena Fernandez, Maria Garcia-Bravo, Carmen Guerra, Lluis Montoliu, Jose Carlos Segovia, Angela M. Valverde, Isabel Fabregat, Blanca Herrera, Aranzazu Sanchez
Summary: Inactivating EGFR signaling in the liver can reduce liver damage and promote efficient regeneration following cholestatic injury. This effect involves enhanced activation of mitogenic/survival signals and changes in cell turnover, which are associated with differences in the profile of intrahepatic immune cells.
JOURNAL OF PATHOLOGY
(2022)
Article
Oncology
Mateo Paz-Cabezas, Tania Calvo-Lopez, Alejandro Romera-Lopez, Daniel Tabas-Madrid, Jesus Ogando, Maria-Jesus Fernandez-Acenero, Javier Sastre, Alberto Pascual-Montano, Santos Manes, Eduardo Diaz-Rubio, Beatriz Perez-Villamil
Summary: This study demonstrates the potential of microRNA profiling in defining colorectal cancer subtypes and identifies microRNA targets associated with a specific subtype. The findings highlight the importance of miRNAs in colorectal cancer stratification and treatment.
Article
Oncology
Francisco Exposito, Miriam Redrado, Maeva Houry, Katherine Hastings, Magdalena Molero-Abraham, Teresa Lozano, Jose Luis Solorzano, Julian Sanz-Ortega, Vera Adradas, Ramon Amat, Esther Redin, Sergio Leon, Naroa Legarra, Javier Garcia, Diego Serrano, Karmele Valencia, Camila Robles-Oteiza, Giorgia Foggetti, Nerea Otegui, Enriqueta Felip, Juan J. Lasarte, Luis Paz-Ares, Jon Zugazagoitia, Katerina Politi, Luis Montuenga, Alfonso Calvo
Summary: Immunotherapy resistance in non-small cell lung cancer (NSCLC) can be attributed to an immunosuppressive microenvironment created by genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression. PTEN-low tumors are associated with higher levels of immune checkpoint proteins and poorer response to immunotherapy. Preclinical models demonstrate that PTEN loss promotes metastasis and fibrosis, and facilitates the conversion of immune cells into immunosuppressive regulatory T cells (Treg). However, targeting PTEN loss-mediated immunosuppression can reverse immunotherapy resistance in NSCLC.
Meeting Abstract
Oncology
E. Conde, S. Hernandez, R. Martinez, J. De Castro, A. Collazo-Lorduy, B. Jimenez, A. Muriel, J. L. Mate, T. Moran, I. Aranda, B. Massuti, F. Rojo, M. Domine, I. Sansano, F. Garcia, E. Felip, N. Mancheno, O. Juan, J. Sanz, J. L. Gonzalez-Larriba, L. Atienza-Cuevas, E. Arriola-Arellano, I. Abdulkader, J. Garcia, C. Camacho, D. Rodriguez-Abreu, C. Teixido, N. Reguart, A. Gonzalez-Pineiro, M. Lazaro-Quintela, M. D. Lozano, A. Gurpide, J. Gomez-Roman, M. Lopez-Brea, L. Pijuan, M. Salido, E. Arriola, A. Company, A. Insa, I. Esteban, M. Saiz, E. Azkona, R. Alvarez, A. Artal, A. B. Enguita, A. Benito, L. Paz-Ares, P. Garrido, F. Lopez-Rios
JOURNAL OF THORACIC ONCOLOGY
(2018)
Article
Cell Biology
Cristina M. Fernandez-Diaz, Luis Escobar-Curbelo, J. F. Lopez-Acosta, Carmen D. Lobaton, Alfredo Moreno, Julian Sanz-Ortega, German Perdomo, Irene Cozar-Castellano
HISTOLOGY AND HISTOPATHOLOGY
(2018)
Review
Pathology
Moushumi Suryavanshi, Julian Sanz-Ortega, Deepika Sirohi, Mukul K. Divatia, Chisato Ohe, Claudia Zampini, Daniel Luthringer, Steven C. Smith, Mahul B. Amin
ADVANCES IN ANATOMIC PATHOLOGY
(2017)
Article
Oncology
Jose Angel Garcia-Saenz, Patricia Ayllon, Marion Laig, Daniel Acosta-Eyzaguirre, Marta Garcia-Esquinas, Myriam Montes, Julian Sanz, Miguel Barquin, Fernando Moreno, Vanesa Garcia-Barberan, Eduardo Diaz-Rubio, Trinidad Caldes, Atocha Romero