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
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
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
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)
Review
Oncology
Javier Ros, Iosune Baraibar, Emilia Sardo, Nuria Mulet, Francesc Salva, Guillem Argiles, Giulia Martini, Davide Ciardiello, Jose Luis Cuadra, Josep Tabernero, Elena Elez
Summary: The development of therapeutic strategies targeting MAPK/ERK and EGFR signaling in BRAF V600E mutated mCRC, with drugs like encorafenib, binimetinib, and cetuximab, has proven successful in improving clinical outcomes. The BEACON trial using these drugs has established a new standard of care in previously treated BRAF V600E mutant mCRC patients, showing impressive improvement in outcomes and tolerable toxicity compared to chemotherapy.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Reyhaneh Moradi-marjaneh, Fereshteh Asgharzadeh, Elnaz Khordad, Mahdi Moradi Marjaneh
Summary: The prognostic value of cfDNA in mCRC patients treated with EGFR inhibitors, particularly in identifying KRAS and BRAF mutations, is highlighted. Assessing mutational status in circulating cell free DNA may offer advantages in patient selection by potentially better representing the dynamicity of tumor genetic status compared to tumor tissue.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Medical Laboratory Technology
Chengfeng Wang, Diling Pan
Summary: This study investigated the relationship between BRAF, KRAS, and PIK3CA mutations and clinicopathologic features and prognosis of colorectal cancer patients. The results showed that the mutant patterns of BRAF, KRAS, and PIK3CA were not associated with the general and clinicopathological features of patients. However, these mutation patterns could be used as independent prognostic factors for colorectal cancer.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Oncology
Ting Xu, Xicheng Wang, Zhenghang Wang, Ting Deng, Changsong Qi, Dan Liu, Yanyan Li, Congcong Ji, Jian Li, Lin Shen
Summary: Multiple genetic alterations are associated with clinical benefits and resistance to EGFR/BRAF inhibitors in BRAF V600E-mutant mCRC. Patients with RNF43 mutations are more likely to achieve clinical benefit from the inhibitors, while genetic alterations in receptor tyrosine kinase genes are associated with worse progression-free survival. Additionally, acquired resistance-related mutations are detected in patients who experienced disease progression.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2022)
Article
Pathology
Seung-Hee Cho, Byung-Joon Seung, Soo-Hyeon Kim, Min-Kyung Bae, Ha-Young Lim, Jung-Hyang Sur
Summary: This study evaluated EGFR expression levels in canine intestinal adenocarcinomas, finding that they were higher than in non-neoplastic tissue at both protein and mRNA levels. Additionally, wild-type sequences were observed in the EGFR, KRAS, and BRAF genes in all 13 samples, aiding in the development of anti-EGFR agents for canine intestinal adenocarcinoma.
VETERINARY PATHOLOGY
(2021)
Review
Oncology
Junjia Liu, Hao Xie
Summary: This review explores the characteristics, clinical relevance, and treatment possibilities of BRAF non-V600 mutations in colorectal cancer, filling in existing knowledge gaps. Understanding the intricacies of these mutations can help healthcare professionals and researchers develop personalized treatment strategies to improve patient care.
Article
Biochemistry & Molecular Biology
Aleksandr S. Martianov, Natalia V. Mitiushkina, Anastasia N. Ershova, Darya E. Martynenko, Mikhail G. Bubnov, Priscilla Amankwah, Grigory A. Yanus, Svetlana N. Aleksakhina, Vladislav I. Tiurin, Aigul R. Venina, Aleksandra A. Anuskina, Yuliy A. Gorgul, Anna D. Shestakova, Mikhail A. Maidin, Alexey M. Belyaev, Liliya S. Baboshkina, Aglaya G. Iyevleva, Evgeny N. Imyanitov
Summary: This study analyzed the factors influencing the distribution of actionable genetic alterations in colorectal carcinomas. The study found that there were differences in the distribution of certain genetic alterations based on patients' age and gender. BRAF mutation frequency also showed geographic variation. In addition, a small fraction of CRCs had simultaneous alterations in more than one driver gene.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Kristiaan J. Lenos, Sander Bach, Leandro Ferreira Moreno, Sanne ten Hoorn, Nina R. Sluiter, Sanne Bootsma, Felipe A. Vieira Braga, Lisanne E. Nijman, Tom van den Bosch, Daniel M. Miedema, Erik van Dijk, Bauke Ylstra, Ruth Kulicke, Fred P. Davis, Nicolas Stransky, Gromoslaw A. Smolen, Robert R. J. Coebergh van den Braak, Jan N. M. IJzermans, John W. M. Martens, Sally Hallam, Andrew D. Beggs, Geert J. P. L. Kops, Nico Lansu, Vivian P. Bastiaenen, Charlotte E. L. Klaver, Maria C. Lecca, Khalid El Makrini, Clara C. Elbers, Mark P. G. Dings, Carel J. M. van Noesel, Onno Kranenburg, Jan Paul Medema, Jan Koster, Lianne Koens, Cornelis J. A. Punt, Pieter J. Tanis, Ignace H. de Hingh, Maarten F. Bijlsma, Jurriaan B. Tuynman, Louis Vermeulen
Summary: A significant proportion of colorectal cancer patients develop peritoneal metastases, which are associated with poor disease outcome. This study characterizes peritoneal metastases from 52 patients and identifies a distinct molecular subtype. The researchers also discover the key role of the structural protein Moesin in peritoneal dissemination and confirm that polyclonal metastatic seeding underlies these lesions.
NATURE COMMUNICATIONS
(2022)
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)
Review
Oncology
Elisa Grassi, Jody Corbelli, Giorgio Papiani, Maria Aurelia Barbera, Federica Gazzaneo, Stefano Tamberi
Summary: 8-12% of patients with advanced colon rectal cancer present with BRAF alterations, particularly the V600E mutation, which is associated with poor prognosis. New therapeutic options, such as targeted therapy combinations, are emerging for this subgroup of patients. Treatment optimization for this subgroup is an important goal.
FRONTIERS IN ONCOLOGY
(2021)
Article
Genetics & Heredity
Peter W. Eide, Seyed H. Moosavi, Ina A. Eilertsen, Tuva H. Brunsell, Jonas Langerud, Kaja C. G. Berg, Bard I. Rosok, Bjorn A. Bjornbeth, Arild Nesbakken, Ragnhild A. Lothe, Anita Sveen
Summary: Gene expression-based subtypes of colorectal cancer have clinical significance, but the representativeness of primary tumors and consensus molecular subtypes (CMS) for metastatic cancers remains unclear. Metastases exhibit decreased CMS1/CMS3 signals and increased CMS4 signals, influenced by the microenvironment. The majority of classified metastases are CMS2 or CMS4, with subtype switching and inter-metastatic CMS heterogeneity being common.
NPJ GENOMIC MEDICINE
(2021)