Article
Multidisciplinary Sciences
Anastasia Samarkina, Markus Kirolos Youssef, Paola Ostano, Soumitra Ghosh, Min Ma, Beatrice Tassone, Tatiana Proust, Giovanna Chiorino, Mitchell P. Levesque, Sandro Goruppi, Gian Paolo Dotto
Summary: Androgen receptor expression is linked to BRAF inhibitor response and targeting AR could be a potential co-therapeutic approach to increase efficacy in melanoma treatment.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Elisa Bonaldi, Chiara Gargiuli, Loris De Cecco, Arianna Micali, Maria Grazia Rizzetti, Angela Greco, Maria Grazia Borrello, Emanuela Minna
Summary: The study demonstrates that the BRAF inhibitors Vemurafenib and Dabrafenib induce antiproliferative and redifferentiative effects in thyroid cancer cells, while rewiring the MAPK pathway related to RAS signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Eslam M. H. Ali, Mohammed S. Abdel-Maksoud, Usama M. Ammar, Karim Mersal, Kyung Ho Yoo, Park Jooryeong, Chang-Hyun Oh
Summary: The study developed and synthesized a series of compounds with anticancer potential, demonstrating promising activity in various cancer types. Two compounds showed notable anti-cancer effects on Melanoma cancer cell lines.
BIOORGANIC CHEMISTRY
(2021)
Review
Oncology
Hiroyuki Takeda, Yu Sunakawa
Summary: BRAF mutations are an important poor prognostic factor in mCRC, but greater understanding of patient characteristics through genomic classification allows for more ideal treatment strategies.
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)
Review
Oncology
Victoria Bouche, Giovanni Aldegheri, Carmine Antonio Donofrio, Antonio Fioravanti, Samuel Roberts-Thomson, Stephen B. Fox, Francesco Schettini, Daniele Generali
Summary: IDH-wild type glioblastoma accounts for the majority of GB cases and has limited therapeutic options. Inhibiting the BRAF pathway shows potential efficacy, but current results are not definitive, requiring further research to better understand treatment response predictors and address limitations in penetrating the blood-brain barrier and developing resistance mechanisms.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Yoshihiro Morimoto, Nami Yamashita, Haruka Hirose, Atsushi Fushimi, Naoki Haratake, Tatsuaki Daimon, Atrayee Bhattacharya, Rehan Ahmad, Yozo Suzuki, Hidekazu Takahashi, Donald W. Kufe
Summary: This study reveals that the BRAF(V600E) mutation in colorectal cancer (CRC) is associated with aggressive disease and resistance to BRAF inhibitors. The expression of MUC1-C protein is significantly upregulated in BRAF(V600E) CRCs. MUC1-C plays a crucial role in promoting cell proliferation and resistance to BRAF inhibitors in BRAF(V600E) CRC cells.
Article
Multidisciplinary Sciences
Jaskaren Kohli, Chen Ge, Eleni Fitsiou, Miriam Doepner, Simone M. Brandenburg, William J. Faller, Todd W. Ridky, Marco Demaria
Summary: Research shows that senescent melanocytes in culture and nevi express high levels of the anti-apoptotic protein BCL-W, but remain insensitive to the pan-BCL-2 inhibitor ABT-263. Resistance to ABT-263 is driven by mTOR-mediated enhanced translation of another anti-apoptotic protein, MCL-1. The combination of ABT-263 and MCL-1 inhibitors results in synthetic lethality to senescent melanocytes, with topical application sufficient to eliminate nevi.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Clemens Cammann, Jonas Kulla, Christian Walz, Fang Zhao, Theresa Lowinus, Eylin Topfstedt, Neha Mishra, Petra Henklein, Ursula Bommhardt, Lukas Bossaller, Christian Hagemeier, Dirk Schadendorf, Boris Schmidt, Annette Paschen, Ulrike Seifert
Summary: The combination of proteasome and Kv1.3 potassium channel inhibitors can inhibit the growth of BRAF-mutant melanoma cells and induce apoptosis. This combination therapy may serve as an alternative approach to treat other tumors expressing mutated BRAF.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Xing Chen, Shan Lin, Ying Lin, Songsong Wu, Minling Zhuo, Ailong Zhang, Junjie Zheng, Zhenhui You
Summary: The study confirmed that BRAF mutation is closely associated with epithelial cell proliferation, apoptosis, and selective autophagy in thyroid cancer patients. Knocking down BRAF-activated WT1 effectively inhibited the proliferation and migration of BRAF(V600E) PTC cells. Silencing WT1 significantly inhibited autophagy and promoted the apoptosis of BRAF(V600E) PTC cells.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Oncology
Monica Capogiri, Andrea J. De Micheli, Alvaro Lassaletta, Denise P. Munoz, Jean-Philippe Coppe, Sabine Mueller, Ana S. Guerreiro S. Stucklin
Summary: BRAF(V600E) is the most common BRAF mutation in human cancers. It is found primarily in pediatric low-grade gliomas (20%), and less frequently in pediatric high-grade gliomas (5-15%) and adult glioblastomas (5%). While BRAF inhibitors have improved clinical care for patients with gliomas, not all patients benefit due to resistance to BRAF inhibition. This review summarizes the current achievements and limitations of BRAF inhibition in gliomas, and discusses potential mechanisms of resistance and future directions for targeted therapy.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Fabrizio Tabbo, Chiara Pisano, Julien Mazieres, Laura Mezquita, Ernest Nadal, David Planchard, Anne Pradines, David Santamaria, Aurelie Swalduz, Chiara Ambrogio, Silvia Novello, Sandra Ortiz-Cuaran
Summary: The emergence of high-throughput sequencing has allowed for a deeper understanding of the molecular characteristics of non-small cell lung cancer, providing better strategies for the treatment of specific BRAF-mutated lung cancers, but there remains a lack of targeted approaches for some patients.
CANCER TREATMENT REVIEWS
(2022)
Article
Multidisciplinary Sciences
Mi-Hyeon You, Min Ji Jeon, Seong ryeong Kim, Woo Kyung Lee, Sheue-yann Cheng, Goo Jang, Tae Yong Kim, Won Bae Kim, Young Kee Shong, Won Gu Kim
Summary: The study revealed that MFN2 may act as a tumor suppressor in thyroid cancer, affecting cell migration and invasion by modulating epithelial to mesenchymal transition.
SCIENTIFIC REPORTS
(2021)
Review
Medicine, General & Internal
Morena Fasano, Carminia Maria Della Corte, Marianna Caterino, Mario Pirozzi, Raffaele Rauso, Teresa Troiani, Giulia Martini, Stefania Napolitano, Floriana Morgillo, Fortunato Ciardiello
Summary: In this case report, a patient with recurrent craniopharyngioma harboring BRAF V600E mutation received targeted therapy with a combination of BRAF inhibitor and MEK inhibitor, showing significant clinical improvement and rapid response.
FRONTIERS IN MEDICINE
(2022)
Article
Endocrinology & Metabolism
Xiao Zhao, Jennifer Rui Wang, Ramona Dadu, Naifa Lamki Busaidy, Lei Xu, Kim O. Learned, Noah N. Chasen, Thinh Vu, Anastasios Maniakas, Arturo A. Eguia, Julia Diersing, Neil D. Gross, Ryan Goepfert, Stephen Y. Lai, Marie-Claude Hofmann, Renata Ferrarotto, Charles Lu, Gary Brandon Gunn, Michael T. Spiotto, Vivek Subbiah, Michelle D. Williams, Maria E. Cabanillas, Mark E. Zafereo
Summary: This study aimed to describe the outcomes of patients with BRAF(V600E)-mutated ATC who received neoadjuvant BRAF-directed therapy followed by surgery. The results showed that neoadjuvant therapy reduced the extent of surgery and surgical morbidity, and patients treated with neoadjuvant therapy had higher overall survival and progression-free survival rates compared to those who didn't have surgery or had surgery before therapy.
Article
Oncology
Hajrah Khawaja, Rebecca Briggs, Cheryl H. Latimer, Mustasin Rassel, Dary Griffin, Lyndsey Hanson, Alberto Bardelli, Frederica Di Nicolantonio, Simon S. McDade, Christopher J. Scott, Shauna Lambe, Manisha Maurya, Andreas U. Lindner, Jochen H. M. Prehn, Jose Sousa, Chris Winnington, Melissa J. LaBonte, Sarah Ross, Sandra Van Schaeybroeck
Summary: Novel covalent inhibitors of KRASG12C have shown limited response rates in patients with KRASG12C-mutant colorectal cancer. In this study, researchers found that the combination of AZ'1569 and a Bcl-xL inhibitor led to a dramatic and universal apoptosis, suggesting a potential therapeutic strategy for patients with KRAS G12C-mutant colorectal cancer.
MOLECULAR CANCER THERAPEUTICS
(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
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
Francesca Bersani, Francesca Picca, Deborah Morena, Luisella Righi, Francesca Napoli, Mariangela Russo, Daniele Oddo, Giuseppe Rospo, Carola Negrino, Barbara Castella, Marco Volante, Angela Listi, Vanessa Zambelli, Federica Benso, Fabrizio Tabbo, Paolo Bironzo, Emanuele Monteleone, Valeria Poli, Filippo Pietrantonio, Federica Di Nicolantonio, Alberto Bardelli, Carola Ponzetto, Silvia Novello, Giorgio V. Scagliotti, Riccardo Taulli
Summary: This study demonstrates that the measurement of circMET levels in the plasma can be used to identify and track patients with high MET activity. It provides a simple, cost-effective, non-invasive approach for implementing patient stratification based on MET expression and monitoring therapy response and clonal evolution during treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(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
Cell Biology
Marta Falcinelli, Giulia Dell'Omo, Elena Grassi, Elisa Mariella, Simonetta Maria Leto, Sharon Scardellato, Annalisa Lorenzato, Sabrina Arena, Andrea Bertotti, Livio Trusolino, Alberto Bardelli, Fabrizio d'Adda di Fagagna
Summary: This study found that colorectal cancer (CRC) does not easily engage in alternative lengthening of telomeres (ALT), even with mutations in ATRX and/or DAXX genes.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Mark Lawler, Lynne Davis, Simon Oberst, Kathy Oliver, Alexander Eggermont, Anna Schmutz, Carlo La Vecchia, Claudia Allemani, Yolande Lievens, Peter Naredi, Tanja Cufer, Ajay Aggarwal, Matti Aapro, Kathi Apostolidis, Anne-Marie Baird, Fatima Cardoso, Andreas Charalambous, Michel P. Coleman, Alberto Costa, Mirjam Crul, Csaba L. Degi, Federica Di Nicolantonio, Sema Erdem, Marius Geanta, Jan Geissler, Jacek Jassem, Beata Jagielska, Bengt Jonsson, Daniel Kelly, Olaf Kelm, Teodora Kolarova, Tezer Kutluk, Grant Lewison, Francoise Meunier, Jana Pelouchova, Thierry Philip, Richard Price, Beate Rau, Isabel T. Rubio, Peter Selby, Maja Juznic Sotlar, Gilliosa Spurrier-Bernard, Jolanda C. van Hoeve, Eduard Vrdoljak, Willien Westerhuis, Urszula Wojciechowska, Richard Sullivan
Summary: Cancer research is vital for improving cancer care, and patients treated in research-active hospitals have better outcomes. However, the COVID-19 pandemic has negatively impacted cancer outcomes in Europe and set back progress by almost a decade. The Lancet Oncology European Groundshot Commission aims to use detailed data on cancer research to inform future cancer care strategies in Europe.