Article
Oncology
Giovanni Randon, Rossana Intini, Chiara Cremolini, Elena Elez, Michael J. Overman, Jeeyun Lee, Paolo Manca, Francesca Bergamo, Filippo Pagani, Maria Antista, Valentina Angerilli, Francisco Javier Ros Montana, Daniele Lavacchi, Alessandra Boccaccino, Giovanni Fuca, Silvia Brich, Laura Cattaneo, Matteo Fassan, Filippo Pietrantonio, Sara Lonardi
Summary: This study aims to investigate the genomic and immunohistochemical expression profiles associated with primary resistance to EGFR/BRAF targeted therapy in patients with BRAF-mutated and microsatellite stable (MSS) metastatic colorectal cancer. The results suggest that the location of the tumor, genomic alterations, and gene expression patterns are associated with resistance to targeted therapy. Patients with a higher tumor mutational burden (TMB) have limited benefits from the treatment and may have worse prognosis.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Yu-Ra Choi, Eun Hye Kang, Sunshin Kim, Seog-Yun Park, Ji-Youn Han, Youngjoo Lee
Summary: This study evaluated the efficacy of single MET inhibition in EGFR-mutant and MET-amplified lung cancer and found that it produced a short-lived response. Further research on novel combination therapy schedules is needed to achieve long-lasting efficacy with less toxicity.
BRITISH JOURNAL OF CANCER
(2023)
Review
Oncology
Valentina Angerilli, Giovanna Sabella, Giovanni Centonze, Sara Lonardi, Francesca Bergamo, Alessandro Mangogna, Filippo Pietrantonio, Matteo Fassan, Massimo Milione
Summary: Molecular biology has greatly increased our understanding of the heterogeneous molecular landscape of colorectal cancer (CRC), with up to 15% of CRC patients harboring the BRAF p.V600E somatic mutation (BRAFmt), a negative prognostic marker in patients with metastatic CRC (mCRC). BRAF mutational testing is now recommended in mCRC patients, but efforts are needed to further stratify patients carrying this mutation.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Review
Oncology
Jennifer Novak, Ravi Salgia, Howard West, Miguel A. Villalona-Calero, Sagus Sampath, Terence Williams, Victoria Villaflor, Erminia Massarelli, Ranjan Pathak, Marianna Koczywas, Brittney Chau, Arya Amini
Summary: In patients with EGFR-mutated NSCLC, continuing TKI therapy despite limited progression of metastatic disease has shown benefits, and radiation therapy to progressive sites of disease can be used to overcome TKI resistance.
Article
Oncology
Jeong Eun Kim, Ji-Hun Kim, Sang-Yeob Kim, Hyungwoo Cho, Yeon-Mi Ryu, Yong Sang Hong, Sun Young Kim, Tae Won Kim
Summary: This study showed that a distinct subgroup of BRAF-MT CRC had a good response to palliative chemotherapy. Higher levels of PD-L1 expression and CD8-positive cell infiltration were associated with better prognosis in BRAF-MT CRC. The immune profile analysis of BRAF-MT tumors can help understand their tumor biology and clinical outcomes better.
Article
Oncology
Ryan J. Hartmaier, Aleksandra A. Markovets, Myung Ju Ahn, Lecia Sequist, Ji-Youn Han, Byoung Chul Cho, Helena A. Yu, Sang-We Kim, James Chih-Hsin Yang, Jong-Seok Lee, Wu-Chou Su, Dariusz M. Kowalski, Sergey Orlov, Song Ren, Paul Frewer, Xiaoling Ou, Darren A. E. Cross, Nisha Kurian, Mireille Cantarini, Pasi A. Jaenne
Summary: Combining MET inhibitor and EGFR tyrosine kinase inhibitor can overcome acquired osimertinib resistance mediated by MET. In this study, savolitinib and osimertinib combination therapy showed promising results in advanced non-small cell lung cancer patients with MET amplification and EGFR mutation who had progressed on prior EGFR-TKI treatment. The combination therapy demonstrated acceptable safety profile and improved antitumor activity.
Review
Biochemistry & Molecular Biology
Elisa Bertoli, Elisa De Carlo, Alessandro Del Conte, Brigida Stanzione, Alberto Revelant, Kelly Fassetta, Michele Spina, Alessandra Bearz
Summary: This article provides a comprehensive review of the emerging molecular resistance mechanism in EGFR-mutated NSCLC pre-treated with osimertinib and its future treatment applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Jen-Hao Yeh, Hsiang-Lin Tsai, Yen-Cheng Chen, Ching-Chun Li, Ching-Wen Huang, Tsung-Kun Chang, Wei-Chih Su, Po-Jung Chen, Yu-Peng Liu, Jaw-Yuan Wang
Summary: Triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in BRAF-mutated metastatic colorectal cancer showed acceptable safety profile and reasonable efficacy in this single-center case series.
MEDICINA-LITHUANIA
(2021)
Review
Biochemistry & Molecular Biology
Ahmad Machmouchi, Laudy Chehade, Sally Temraz, Ali Shamseddine
Summary: Targeted monoclonal antibody therapy against EGFR is a leading treatment for mCRC. However, resistance due to KRAS and BRAF mutations has emerged. Cells with these mutations overexpress GLUT1 and SVCT2, leading to intracellular vitamin C transport and cell death. High dose vitamin C shows promise in overcoming EGFR resistance in mCRC with wild KRAS mutation and in patients with KRAS and BRAF mutations, but more clinical trials are needed.
Article
Genetics & Heredity
Biao Huang, Wenxing Su, Daojiang Yu
Summary: This study investigates the immune infiltration and prognostic biomarkers in patients with BRAF mutated skin cutaneous melanoma. The results suggest that dysregulation of immune function and immune cells may contribute to poor outcomes in these patients.
FRONTIERS IN GENETICS
(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.
Article
Oncology
Boning Cai, Xiaomo Li, Xiang Huang, Tonghui Ma, Baolin Qu, Wei Yu, Wei Yang, Pei Zhang, Jing Chen, Fang Liu
Summary: EGFR tyrosine kinase inhibitors are standard treatment for NSCLC patients, but resistance is common. Combination of EGFR and MET inhibitors has shown promise, but acquired resistance to MET inhibitors is a challenge. Sequential MET inhibitor use may be effective for EGFR-mutant, MET-amplified NSCLC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Emilie Hafliger, Alessandra Boccaccino, Alexandra Lapeyre-Prost, Audrey Perret, Claire Gallois, Maria Antista, Lorenzo Pilla, Thierry Lecomte, Mario Scartozzi, Emilie Soularue, Lisa Salvatore, Vincent Bourgeois, Massimiliano Salati, David Tougeron, Ludovic Evesque, Jean-Nicolas Vaillant, Reem El-Khoury, Sara Lonardi, Chiara Cremolini, Julien Taieb
Summary: The combination of anti-BRAF and anti-EGFRs shows efficacy in patients with BRAFm mCRC previously treated with an anti-EGFR agent. The results of this retrospective study suggest that this combination could be a valuable treatment option for patients with limited therapeutic alternatives.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Matteo Fassan, Massimo Milione, Giulia Maddalena, Chiara Cremolini, Marta Schirripa, Filippo Pietrantonio, Nicoletta Pella, Emanuela Dell'Aquila, Elisa Sperti, Clizia Zichi, Francesca Bergamo, Marco Volante, Alessandra Boccaccino, Federica Morano, Francesco Cortiula, Giovanna De Maglio, Lorenza Rimassa, Valeria Smiroldo, Lorenzo Calvetti, Giuseppe Aprile, Lisa Salvatore, Daniele Santini, Roberta Salmaso, Giovanni Centonze, Paola Biason, Chiara Borga, Sara Lonardi, Vittorina Zagonel, Angelo P. Dei Tos, Massimo Di Maio, Fotios Loupakis
Summary: Neuroendocrine differentiation in BRAFmt metastatic colorectal cancers is associated with worse prognosis in terms of progression-free survival (PFS) and overall survival (OS). Further studies are needed to investigate the molecular mechanisms underlying the acquisition of neuroendocrine phenotype for potential novel-targeted treatment strategies.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Edyta M. Urbanska, Morten Grauslund, Peter R. Koffeldt, Sarah L. B. Truelsen, Johan O. Loefgren, Junia C. Costa, Linea C. Melchior, Jens B. Sorensen, Eric Santoni-Rugiu
Summary: Amplification of the MET gene is a mechanism of acquired resistance to EGFR-TKIs in patients with EGFR-mutated NSCLC. It can also occur de novo and cause intrinsic resistance. There are no standard therapies for these patients, but combinations of EGFR-TKIs with Crizotinib may be effective. However, the co-occurrence of other genomic and phenotypic alterations can impact the response to this combination. Different diagnostic methods should be used together to accurately detect MET amplification. The addition of Crizotinib to EGFR-TKI treatment has shown reasonable efficacy in patients with MET amplification, with a progression-free survival of 3-19 months.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Paolo Corradini, Chiara Agrati, Giovanni Apolone, Alberto Mantovani, Diana Giannarelli, Vincenzo Marasco, Veronica Bordoni, Alessandra Sacchi, Giulia Matusali, Carlo Salvarani, Pier Luigi Zinzani, Renato Mantegazza, Fabrizio Tagliavini, Maria Teresa Lupo-Stanghellini, Fabio Ciceri, Silvia Damian, Antonio Uccelli, Daniela Fenoglio, Nicola Silvestris, Fausto Baldanti, Giulia Piaggio, Gennaro Ciliberto, Aldo Morrone, Franco Locatelli, Valentina Sinno, Maria Rescigno, Massimo Costantini
Summary: This study investigated the immune response to the SARS-CoV-2 vaccine in patients with tumors and immune disorders. The results showed that immunosuppressive treatment was a risk factor for a low humoral response, while the booster dose improved both humoral and T-cell responses.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Oncology
Vito Amodio, Simona Lamba, Rosaria Chila, Chiara M. Cattaneo, Benedetta Mussolin, Giorgio Corti, Giuseppe Rospo, Enrico Berrino, Claudio Tripodo, Federica Pisati, Alice Bartolini, Maria Costanza Aquilano, Silvia Marsoni, Gianluca Mauri, Caterina Marchio, Sergio Abrignani, Federica Di Nicolantonio, Giovanni Germano, Alberto Bardelli
Summary: Patients with DNA mismatch repair deficiency (MMRd) in colorectal cancer (CRC) often respond to immune checkpoint blockade therapies, while those with mismatch repair-proficient (MMRp) tumors generally do not. MMRp CRCs with variable fractions of MMRd cells may impact immune surveillance. Modulation of the MMRd fraction in MMR heterogeneous tumors can enhance their immunogenicity.
Article
Oncology
Francesca Orzan, Francesca De Bacco, Elisabetta Lazzarini, Giovanni Crisafulli, Alessandra Gasparini, Angelo Dipasquale, Ludovic Barault, Marco Macagno, Pasquale Persico, Federico Pessina, Beatrice Bono, Laura Giordano, Pietro Zeppa, Antonio Melcarne, Paola Cassoni, Diego Garbossa, Armando Santoro, Paolo M. Comoglio, Stefano Indraccolo, Matteo Simonelli, Carla Boccaccio
Summary: In this study, the use of cerebrospinal fluid (CSF) for molecular characterization of newly diagnosed gliomas was investigated. It was found that tumor DNA is abundant in CSF close to the tumor, but mostly below detection threshold in CSF collected by lumbar puncture. However, in over 60% of lumbar puncture CSF samples, tumor DNA was sufficient to assess the main molecular subtypes of gliomas.
CLINICAL CANCER RESEARCH
(2023)
Article
Pathology
Enrico Berrino, Maria Costanza Aquilano, Emanuele Valtorta, Vito Amodio, Giovanni Germano, Marco Gusmini, Katiuscia Gizzi, Elisabetta Fenocchio, Anna Sapino, Silvia Marsoni, Andrea Sartore-Bianchi, Alberto Bardelli, Salvatore Siena, Emanuela Bonoldi, Caterina Marchio
Summary: Colorectal cancer cells often exhibit homogeneous retention or loss of mismatch repair (MMR) protein expression, but rare cases show heterogeneous patterns. In this study, 200 colorectal cancers were analyzed for MMR protein expression, resulting in three groups: proficient MMR, deficient MMR, and heterogeneous MMR expression. Heterogeneous MMR tumors were further examined and compared to the other groups, revealing differential gene expression patterns and increased tumor-infiltrating lymphocytes.
Article
Endocrinology & Metabolism
Giovanni Centonze, Patrick Maisonneuve, Natalie Prinzi, Sara Pusceddu, Luca Albarello, Eleonora Pisa, Massimo Barberis, Alessandro Vanoli, Paola Spaggiari, Paola Bossi, Laura Cattaneo, Giovanna Sabella, Enrico Solcia, Stefano La Rosa, Federica Grillo, Giovanna Tagliabue, Aldo Scarpa, Mauro Papotti, Marco Volante, Alessandro Mangogna, Alessandro Del Gobbo, Stefano Ferrero, Luigi Rolli, Elisa Roca, Luisa Bercich, Mauro Benvenuti, Luca Messerini, Frediano Inzani, Giancarlo Pruneri, Adele Busico, Federica Perrone, Elena Tamborini, Alessio Pellegrinelli, Ketevani Kankava, Alfredo Berruti, Ugo Pastorino, Nicola Fazio, Fausto Sessa, Carlo Capella, Guido Rindi, Massimo Milione
Summary: This study analyzed a large series of neuroendocrine carcinomas (NECs) to validate previously identified prognostic factors and determine if additional parameters could be isolated. The most relevant predictors for prognosis were Ki-67 index, morphology, stage, and site. However, morphology was not a significant factor when Ki-67 was greater than or equal to 55%.
NEUROENDOCRINOLOGY
(2023)
Article
Immunology
Maria Rescigno, Chiara Agrati, Carlo Salvarani, Diana Giannarelli, Massimo Costantini, Alberto Mantovani, Raffaella Massafra, Pier Luigi Zinzani, Aldo Morrone, Stefania Notari, Giulia Matusali, Giuseppe Lauria Pinter, Antonio Uccelli, Gennaro Ciliberto, Fausto Baldanti, Franco Locatelli, Nicola Silvestris, Valentina Sinno, Elena Turola, Maria Teresa Lupo-Stanghellini, Giovanni Apolone
Summary: This study compared the B-cell, T-cell, and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus in patients with hematological malignancies, solid tumors, and immune-rheumatological diseases after the fourth dose of mRNA COVID-19 vaccine. The T-cell response was similarly boosted by the fourth dose across different subgroups, while the antibody response was improved only in patients not receiving B-cell targeted therapies. However, a small percentage of patients did not have neutralizing antibodies to either virus variants, making them vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine. Additional booster doses are recommended for frail patients to enhance the development of a B-cell response against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Arsela Prelaj, Edoardo Gregorio Galli, Vanja Miskovic, Mattia Pesenti, Giuseppe Viscardi, Benedetta Pedica, Laura Mazzeo, Achille Bottiglieri, Leonardo Provenzano, Andrea Spagnoletti, Roberto Marinacci, Alessandro De Toma, Claudia Proto, Roberto Ferrara, Marta Brambilla, Mario Occhipinti, Sara Manglaviti, Giulia Galli, Diego Signorelli, Claudia Giani, Teresa Beninato, Chiara Carlotta Pircher, Alessandro Rametta, Sokol Kosta, Michele Zanitti, Maria Rosa Di Mauro, Arturo Rinaldi, Settimio Di Gregorio, Martinetti Antonia, Marina Chiara Garassino, Filippo G. M. de Braud, Marcello Restelli, Giuseppe Lo Russo, Monica Ganzinelli, Francesco Trovo, Alessandra Laura Giulia Pedrocchi
Summary: In this study, a model was developed using explainable AI machine learning methods to accurately predict the efficacy of immunotherapy in advanced non-small cell lung cancer patients. The study found that the neutrophil to lymphocyte ratio was an important feature influencing the model's predictions.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Erica Torchiaro, Consalvo Petti, Sabrina Arena, Francesco Sassi, Giorgia Migliardi, Alfredo Mellano, Roberta Porporato, Marco Basirico, Loretta Gammaitoni, Enrico Berrino, Monica Montone, Giorgio Corti, Giovanni Crisafulli, Caterina Marchio, Alberto Bardelli, Enzo Medico
Summary: High-grade mucinous colorectal cancer (HGM CRC) is an aggressive subtype that is difficult to treat, often accompanied by signet ring cancer cells. The development of patient-derived preclinical models for this subtype is crucial in oncology. In this study, successful propagation of preclinical models from a Lynch syndrome patient with refractory HGM CRC was achieved, providing a valuable tool for exploring alternative treatments. Inhibition of the proteasome by bortezomib and the NEDD8 pathway by pevonedistat showed promising results in both in vitro and in vivo testing, highlighting their potential as effective therapeutic approaches against Lynch syndrome-associated HGM CRC.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Valentina Comunanza, Chiara Gigliotti, Simona Lamba, Gabriella Doronzo, Edoardo Vallariello, Valentina Martin, Claudio Isella, Enzo Medico, Alberto Bardelli, Dario Sangiolo, Federica Di Nicolantonio, Federico Bussolino
Summary: The introduction of targeted therapies has greatly improved the treatment of BRAFV600E melanoma, but acquired resistance remains a challenge. This study explored the strategy of VEGFA/BRAF inhibition in immunocompetent melanoma murine models and found that it reshaped the tumor microenvironment, enhanced immune cell infiltration, and sensitized tumors to immune checkpoint blockade. Combining VEGFA/BRAF targeting with anti-PD-1 antibody resulted in a durable response and complete tumor eradication in 50% of the mice.
MOLECULAR ONCOLOGY
(2023)
Editorial Material
Oncology
Federica Di Nicolantonio, Alberto Bardelli
Summary: Allele-specific inhibitors of KRAS(G12C) have been approved for non-small-cell lung cancer. This article discusses recent results from the phase I/II KRYSTAL-1 trial of adagrasib alone and in combination with cetuximab in patients with KRAS(G12C)-mutant metastatic colorectal cancer. The combination treatment showed promising efficacy and, if confirmed in later-phase trials, simultaneous inhibition of EGFR and KRAS(G12C) will introduce a new paradigm in precision oncology.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Oncology
Emma Zattarin, Daniele Presti, Luigi Mariani, Caterina Sposetti, Rita Leporati, Alice Menichetti, Chiara Corti, Chiara Benvenuti, Giovanni Fuca, Riccardo Lobefaro, Francesca Ligorio, Leonardo Provenzano, Andrea Vingiani, Marta Del Vecchio, Gaia Griguolo, Marianna Sirico, Ottavia Bernocchi, Antonio Marra, Paola Zagami, Elisa Agostinetto, Flavia Jacobs, Pierluigi Di Mauro, Andrea Esposito, Carlo Alberto Giorgi, Luca Lalli, Laura Boldrini, Pier Paolo Berton Giacchetti, Ambra Carnevale Schianca, Valentina Guarneri, Rebecca Pedersini, Agnese Losurdo, Alberto Zambelli, Daniele Generali, Carmen Criscitiello, Giuseppe Curigliano, Giancarlo Pruneri, Filippo de Braud, Maria Vittoria Dieci, Claudio Vernieri
Summary: In 428 patients with HR+/HER2- advanced breast cancer, HER2-low status was found to be independently associated with worse progression-free survival (PFS) and overall survival (OS) compared to HER2-0 status. These findings suggest that HER2-low status could serve as a new prognostic biomarker in this clinical setting.
Article
Oncology
Leonardo Provenzano, Riccardo Lobefaro, Francesca Ligorio, Emma Zattarin, Luca Zambelli, Caterina Sposetti, Daniele Presti, Giulia Montelatici, Angela Ficchi, Antonia Martinetti, Alessio Arata, Marta Del Vecchio, Claudia Lauria Pantano, Barbara Formisano, Giulia Valeria Bianchi, Giuseppe Capri, Filippo de Braud, Claudio Vernieri, Giovanni Fuca
Summary: The study aims to test the prognostic ability of a novel inflammatory biomarker, the pan-immune-inflammation value (PIV), based on complete blood count (CBC), in patients with advanced triple-negative breast cancer (aNBC) who received first-line platinum-based chemotherapy. The results showed that PIV could serve as a prognostic factor and is associated with the efficacy of chemotherapy.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2023)
Article
Oncology
Stefano Cavalieri, Viviana Vitolo, Amelia Barcellini, Sara Ronchi, Angelica Facoetti, Chiara Campo, Catherine Klersy, Silvia Molinelli, Francesco Agustoni, Virginia Valeria Ferretti, Annalisa De Silvestri, Marco Platania, Michele Del Vecchio, Marco Durante, Alexander Helm, Claudia Fournier, Filippo de Braud, Paolo Pedrazzoli, Ester Orlandi, Lisa Licitra
Summary: ICONIC is a phase II clinical trial that aims to assess the feasibility and clinical activity of combining carbon ion radiotherapy with immune checkpoint inhibitors in cancer patients. This study will provide controlled data regarding the safety of this novel therapeutic combination, as no previous clinical trials have evaluated it.
Article
Hematology
Cristina Verzeroli, Cinzia Giaccherini, Laura Russo, Silvia Bolognini, Sara Gamba, Carmen J. Tartari, Francesca Schieppati, Chiara Ticozzi, Alfonso Vignoli, Giovanna Masci, Roberta Sarmiento, Daniele Spinelli, Paolo Malighetti, Carlo Tondini, Fausto Petrelli, Francesco Giuliani, Andrea D'Alessio, Giampietro Gasparini, Mauro Minelli, Filippo De Braud, Armando Santoro, Roberto Labianca, Marina Marchetti, Anna Falanga
Summary: This study assessed the risk of VTE and mortality within 6 months and found that both the KRS and the new-Vienna CATS risk scores showed similar discriminating potential. However, after the application of cut-off values, the new-Vienna CATS score provided statistically significant stratification for VTE. Both RAMs proved to be effective in identifying patients at increased risk of mortality.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)