Review
Oncology
A. Grothey, M. Fakih, J. Tabernero
Summary: Colorectal cancer remains a leading cause of cancer-related deaths globally, with the mutation in the BRAF gene, particularly the V600E substitution, affecting 10% of metastatic CRC patients and indicating a poor prognosis. Recent advancements in combination therapies targeting the MAPK pathway have shown promising results in treating BRAF V600E-mutated mCRC patients, offering new hope in the management of this subtype of cancer.
ANNALS OF ONCOLOGY
(2021)
Review
Oncology
Gianluca Mauri, Erica Bonazzina, Alessio Amatu, Federica Tosi, Katia Bencardino, Viviana Gori, Daniela Massihnia, Tiziana Cipani, Francesco Spina, Silvia Ghezzi, Salvatore Siena, Andrea Sartore-Bianchi
Summary: The BRAF(V600E) mutation is detected in 8-10% of patients with metastatic colorectal cancer (mCRC) and has a poor prognostic outlook, with median overall survival below 20 months. Treatment options include immune checkpoint inhibitors (CPIs) for those with concomitant MSI-H status, and a combination of cytotoxic chemotherapy + anti-VEGF or EGFR and BRAF inhibitors for first and second line treatment, respectively. However, acquired resistance limits the potential benefits and survival remains poor. Ongoing clinical trials are exploring various strategies to improve treatment outcomes for this subset of patients.
Review
Oncology
Maria Grazia Rodriquenz, Davide Ciardiello, Tiziana Pia Latiano, Brigida Anna Maiorano, Erika Martinelli, Nicola Silvestris, Fortunato Ciardiello, Evaristo Maiello
Summary: Approximately 8-15% of patients with metastatic colorectal cancer (mCRC) have mutation in the BRAF gene. Recent advances in molecular biology have improved our understanding of the molecular heterogeneity within BRAF mutant (BRAFMT) CRCs, including the high rate of overlapping with MSI-H status and the presence of non-V600E mutations associated with better behavior. Treatment options for this subgroup have expanded, but the development of secondary resistance remains a major challenge.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Oncology
Ting Xu, Jian Li, Zhenghang Wang, Xiaotian Zhang, Jun Zhou, Zhihao Lu, Lin Shen, Xicheng Wang
Summary: This study retrospectively analyzed the clinical data of patients between June 2010 and December 2021 and found an association between BRAF V600E mutation and poor and heterogeneous prognosis. First-line intensive chemotherapy had limited impact on progression-free survival and overall survival in patients with BRAF V600E mutant metastatic colorectal cancer.
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
Biochemistry & Molecular Biology
Chune Yu, Dan Luo, Jing Yu, Min Zhang, Xiaobo Zheng, Guangchao Xu, Jiaxin Wang, Huiling Wang, Yufei Xu, Ke Jiang, Jie Xu, Xuelei Ma, Jing Jing, Hubing Shi
Summary: The study identified GRB7-PLK1 as a crucial axis mediating RTKs, resulting in tolerance to MEK inhibitors. Therefore, PLK1 is a promising target for enhancing the clinical treatment of CRC patients with KRAS mutations by synergizing with MEK inhibitors.
Article
Oncology
Gregory J. Riely, Egbert F. Smit, Myung-Ju Ahn, Enriqueta Felip, Suresh S. Ramalingam, Anne Tsao, Melissa Johnson, Francesco Gelsomino, Raymond Esper, Ernest Nadal, Michael Offin, Mariano Provencio, Jeffrey Clarke, Maen Hussain, Gregory A. Otterson, Ibiayi Dagogo-Jack, Jonathan W. Goldman, Daniel Morgensztern, Ann Alcasid, Tiziana Usari, Paul Wissel, Keith Wilner, Nuzhat Pathan, Svitlana Tonkovyd, Bruce E. Johnson
Summary: The combination of encorafenib and binimetinib showed clinical efficacy and acceptable safety in patients with BRAF(V600E)-mutant metastatic NSCLC.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Rong Wang, Hong-xin Yang, Jie Chen, Jian-jun Huang, Qing Lv
Summary: This meta-analysis suggests that breast surgery (including modified radical mastectomy and breast-conserving surgery) combined with radiotherapy may be the optimal surgical approach in patients with occult breast cancer. Radiotherapy does not prolong the time of distant metastasis and local recurrences.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Marta Fudalej, Daria Kwasniewska, Pawel Nurzynski, Anna Badowska-Kozakiewicz, Dominika Mekal, Aleksandra Czerw, Katarzyna Sygit, Andrzej Deptala
Summary: Poor prognosis of pancreatic cancer (PC) is associated with several factors, such as diagnosis at an advanced stage, early distant metastases, and remarkable resistance to most conventional treatment options. The pathogenesis of PC seems to be significantly more complicated than originally assumed. To develop effective treatment schemes prolonging patient survival, a multidirectional approach encompassing different aspects of the cancer is needed. Further studies bringing together different therapeutic strategies are required. This review provides an overview of new or emerging therapeutic strategies for the more effective management of metastatic PC.
Review
Oncology
Erika Martinelli, Dirk Arnold, Andres Cervantes, Sebastian Stintzing, Eric Van Cutsem, Josep Tabernero, Julien Taieb, Harpreet Wasan, Fortunato Ciardiello
Summary: This article reviews the current knowledge and consensus management on the clinical management of BRAFV600E-mutant metastatic colorectal cancer (mCRC). The treatment landscape for this specific type of mCRC has changed greatly due to the emergence of molecular targeted therapies and immune checkpoint inhibitors. Tumor tissue analysis for DNA mismatch repair/microsatellite status and KRAS, NRAS, and BRAF mutational status is mandatory for appropriate clinical management and treatment decisions.
CANCER TREATMENT REVIEWS
(2023)
Article
Oncology
E. Martinelli, C. Cremolini, T. Mazard, J. Vidal, I Virchow, D. Tougeron, P-J Cuyle, B. Chibaudel, S. Kim, I Ghanem, B. Asselain, C. Castagne, A. Zkik, S. Khan, D. Arnold
Summary: This study is the largest real-world analysis to date of patients with BRAF(V600E) mutant mCRC, providing valuable insights into routine first-line treatment practices for these patients. The results highlight the intrinsic aggressiveness of this disease subgroup and emphasize the urgent need for more effective treatment options in this setting.
Review
Oncology
Verane Achard, Paul Martin Putora, Aurelius Omlin, Thomas Zilli, Stefanie Fischer
Summary: Metastatic prostate cancer treatment has shifted with the introduction of novel therapeutic agents, requiring clinicians to choose the most appropriate treatment combination and sequence for each patient based on individual factors to optimize efficacy.
Article
Nanoscience & Nanotechnology
Ayimukedisi Yalikong, Xu-Quan Li, Ping-Hong Zhou, Zhi-Peng Qi, Bing Li, Shi-Lun Cai, Yun-Shi Zhong
Summary: The HER2-targeted nanoparticles (TPLNP) drug delivery system has shown significant anti-tumor effects on colon cancer with HER2 overexpression and BRAF mutation in preclinical models, suggesting promising potential for clinical application.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Article
Oncology
Sebastian Stintzing, Kathrin Heinrich, David Tougeron, Dominik Paul Modest, Ingo Schwaner, Jan Eucker, Rudolf Pihusch, Martina Stauch, Florian Kaiser, Christoph Kahl, Meinolf Karthaus, Christian Mueller, Christof Burkart, Anke Reinacher-Schick, Stefan Kasper-Virchow, Ludwig Fischer von Weikersthal, Beate Krammer-Steiner, Gerald Wolfgang Prager, Julien Taieb, Volker Heinemann
Summary: This clinical trial investigated the efficacy of triplet chemotherapy combined with either cetuximab or bevacizumab in previously untreated BRAF(V600E)-mutant metastatic colorectal cancer (mCRC) patients. The results showed that bevacizumab-based chemotherapy remains the preferable first-line treatment for patients with BRAF(V600E)-mutant mCRC.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Georgios Solomou, Alina Finch, Asim Asghar, Chiara Bardella
Summary: Altered metabolism is observed in many cancers, including gliomas, due to mutations in metabolic genes like isocitrate dehydrogenase (IDH). Mutant IDH converts α-ketoglutarate (α-KG) to D2-hydroxyglutarate (D2-HG) instead of isocitrate. Accumulation of D2-HG in IDH mutant tumors has led to the development of small inhibitors to target mutant IDH. This review summarizes the cellular and molecular consequences of IDH mutations and therapeutic approaches for IDH mutant tumors, with a focus on gliomas.
Article
Gastroenterology & Hepatology
Olivier Caliez, Daniel Pietrasz, Feryel Ksontini, Solene Doat, Jean-Marc Simon, Jean-Christophe Vaillant, Valerie Taly, Pierre Laurent-Puig, Jean-Baptiste Bachet
Summary: This study aimed to investigate the impact of baseline circulating tumor DNA status on treatment and prognosis of patients with borderline resectable or locally advanced pancreatic adenocarcinoma. The results showed that positive baseline ctDNA was associated with shorter progression-free survival and shorter relapse-free survival after secondary resection.
DIGESTIVE AND LIVER DISEASE
(2022)
Article
Oncology
Guillaume Beinse, Marie-Aude Le Frere Belda, Pierre-Alexandre Just, Nahina Bekmezian, Meriem Koual, Simon Garinet, Karen Leroy, Franck Letourneur, Adele Lusson, Claire Mulot, Delphine Le Corre, Marie Metairie, Nicolas Delanoy, Helene Blons, Claire Gervais, Catherine Durdux, Charles Chapron, Francois Goldwasser, Benoit Terris, Cecile Badoual, Valerie Taly, Pierre Laurent-Puig, Bruno Borghese, Anne-Sophie Bats, Jerome Alexandre
Summary: This study aimed to evaluate the classification ability of RNA sequencing (RNA-seq) for prognosis prediction in endometrial carcinoma (EC) patients. The results showed that RNA-seq can provide additional prognostic information beyond established classification systems and has potential applications in therapeutic strategies for EC.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Pathology
Xanthi Stachtea, Maurice B. Loughrey, Manuela Salvucci, Andreas U. Lindner, Sanghee Cho, Elizabeth McDonough, Anup Sood, John Graf, Alberto Santamaria-Pang, Alex Corwin, Pierre Laurent-Puig, Sonali Dasgupta, Jinru Shia, Jonathan R. Owens, Samantha Abate, Sandra Van Schaeybroeck, Mark Lawler, Jochen H. M. Prehn, Fiona Ginty, Daniel B. Longley
Summary: In this study, immune signatures in the tumor and tumor microenvironment were assessed using a multiplexed immunofluorescence imaging technology, revealing a significant association between regulatory T cells (Tregs) and survival rates in colorectal cancer patients. Multi-marker classification provided more accurate quantitation of immune cell types with stronger correlations with patient outcomes compared to single markers.
Article
Gastroenterology & Hepatology
Raef Abdallah, Shulin Zhao, Simon Garinet, Katia Hormigos, Delphine Le Corre, Jerome Cros, Karla Perez Toralla, Anne Sophie Bats, Jeremy Augustin, Jean-Baptiste Bachet, Valerie Taly, Helene Blons, Julien Taieb, Pierre Laurent-Puig
Summary: This study demonstrates that HRD gene promoter methylation events are rare in European patients with pancreatic adenocarcinoma.
CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY
(2022)
Article
Medical Laboratory Technology
Guillaume Beinse, Bruno Borghese, Marie Metairie, Pierre-Alexandre Just, Geoffroy Poulet, Simon Garinet, Beatrice Parfait, Audrey Didelot, Camille Bourreau, Natacha Agueeff, Alexandre Lavolle, Benoit Terris, Charles Chapron, Francois Goldwasser, Karen Leroy, Helene Blons, Pierre Laurent-Puig, Valerie Taly, Jerome Alexandre
Summary: This study aimed to identify DNA positions universally hypermethylated in endometrial carcinoma (EC) and develop a digital droplet PCR (ddPCR) assay for detection of hypermethylated circulating tumor DNA (meth-ctDNA) in plasma from EC patients. The study found that methylation of ZSCAN12/OXT can be highly specific and sensitive in detecting ctDNA in plasma, providing promise for personalized approaches for EC patients.
CLINICAL CHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Emeric Boisteau, Eric Francois, Thomas Aparicio, Karine Le Malicot, Rabia Boulahssass, Thierry Lecomte, Pierre Laurent-Puig, Boris Guiu, Elena Paillaud, Marie-Pierre Galais, Daniel Lopez-Trabada Ataz, David Tougeron, Louis-Marie Dourthe, Rosine Guimbaud, Emmanuelle Samalin, Marie Moreau, Christophe Louvet, Come Lepage, Astrid Lievre
Summary: The study aims to evaluate the impact of second-line Ramucirumab alone or combined with Paclitaxel on overall survival and quality of life in patients over 70 years old with advanced gastric cancer.
DIGESTIVE AND LIVER DISEASE
(2022)
Article
Gastroenterology & Hepatology
Violaine Randrian, Simon Pernot, Karine Le Malicot, Vittorio Catena, Isabelle Baumgaertner, Vania Tacher, Julien Forestier, Vincent Hautefeuille, Claire Tabouret-Viaud, Alice Gagnaire, Emmanuel Mitry, Boris Guiu, Thomas Aparicio, Denis Smith, Anthony Dhomps, Jean-Pierre Tasu, Remy Perdrisot, Julien Edeline, Claude Capron, Catherine Cheze-Le Rest, Jean-Francois Emile, Pierre Laurent-Puig, Theodora Bejan-Angoulvant, Harry Sokol, Come Lepage, Julien Taieb, David Tougeron
Summary: By combining selective internal radiation therapy and medication, the sensitivity of microsatellite stable metastatic colorectal cancer to immune checkpoint inhibitors can be enhanced.
DIGESTIVE AND LIVER DISEASE
(2022)
Article
Oncology
Catherine Conti, Frederic Pamoukdjian, Thomas Aparicio, Soraya Mebarki, Johanne Poisson, Gilles Manceau, Julien Taieb, Bastien Rance, Sandrine Katsahian, Anais Charles-Nelson, Elena Paillaud
Summary: This study aims to investigate the prognostic factors and chemotherapy efficacy in older patients (≥70 years) with metastatic pancreatic cancer (mPC). The results showed that gemcitabine + nab-paclitaxel regimen and anti-diabetic therapy were associated with better overall survival, while impaired functional status, liver metastases, and high neutrophil count were associated with worse overall survival.
Article
Medicine, General & Internal
Thomas Helmberger, Pierleone Lucatelli, Philippe L. Pereira, Aleksandar Gjoreski, Ivona Jovanoska, Zoltan Bansaghi, Stavros Spiliopoulos, Francesca Carchesio, Dirk Arnold, Andreas Baierl, Bleranda Zeka, Nathalie C. Kaufmann, Julien Taieb, Roberto Iezzi
Summary: CIREL is an observational study aiming to assess the feasibility and tolerability of LP-irinotecan TACE for unresectable colorectal cancer liver metastases. The study showed a technical success rate of 99% and a high completion rate of planned treatment sessions. The occurrence of AEs was related to liver involvement, bilobar disease, and the size of beads used.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Marie Auvray Kuentz, Helene Blons, Anne Paule Gimenez-Roqueplo, Just Pierre-Alexandre, Pierre Laurent-Puig, Arnaud Mejean, Stephane Oudard, Virginie Verkarre
Summary: This study identified a new VCP::TFE3 fusion gene caused by a t(X;9)(p11.23;p13.3) translocation through whole transcriptome sequencing. The patient showed typical morphological features of TFE3-rearranged RCC and demonstrated positive TFE3 immunostaining and break-apart fluorescence in situ hybridization. The patient received surgery and five lines of therapy, including 24 months of stable disease with the MET inhibitor cabozantinib, resulting in an overall survival of 7 years. Besides expanding the spectrum of TFE3 rearrangement partners, this study emphasizes the complexity of these tumors and supports the development of translational programs in renal cancer.
GENES CHROMOSOMES & CANCER
(2023)
Article
Biochemistry & Molecular Biology
Roseline Vibert, Jasmine Hasnaoui, Alexandre Perrier, Alexandra Lefebvre, Chrystelle Colas, Marion Dhooge, Noemie Basset, Albain Chansavang, Camille Desseignes, Alex Duval, Solenne Farelly, Nadim Hamzaoui, Pierre Laurent-Puig, Julie Metras, Diane Moliere, Martine Muleris, Jeanne Netter, Mehdi Touat, Franck Bielle, Karim Labreche, Romain Nicolle, Geraldine Perkins, Mathilde Warcoin, Florence Coulet, Patrick R. Benusiglio
Summary: Some patients with Lynch syndrome (LS) exhibit extreme phenotypes, such as cancer at an early age or cancer types without screening guidelines. This study investigated the role of additional germline variants in cancer susceptibility genes (CSG) in explaining these phenotypes. Comparison of LS patients with early-onset (EO) and usual-onset (UO) cancer diagnoses revealed an excess of pathogenic variants and variants of unknown significance in the gastrointestinal CSG for the EO group. Notable germline variants were identified, suggesting the consideration of additional variants in future screening recommendations to better assess cancer risk.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Medicine, Research & Experimental
Simon Garinet, Audrey Didelot, Laetitia Marisa, Guillaume Beinse, Marine Sroussi, Francoise Le Pimpec-Barthes, Elizabeth Fabre, Laure Gibault, Pierre Laurent-Puig, Sophie Mouillet-Richard, Antoine Legras, Helene Blons
Summary: We identified a miR-200 based RNA signature that can distinguish the heterogeneity of Epithelial-to-mesenchymal transition (EMT) and predict the survival of lung adenocarcinoma patients. This signature can stratify patients into high- and low-risk groups independently of tumor stage for prognostic evaluation.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Julia Kaellberg, Alexandra Harrison, Valerie March, Santa Berzina, Ivan Nemazanyy, Oliver Kepp, Guido Kroemer, Sophie Mouillet-Richard, Pierre Laurent-Puig, Valerie Taly, Wenjin Xiao
Summary: The high mortality rate in colorectal cancer (CRC) is mainly due to drug resistance caused by intratumor heterogeneity (ITH). This study investigated the interaction between different molecular subtypes of CRC cells and found that coculturing CMS1 and CMS4 cells increased their resistance to the chemotherapeutic agent 5-fluorouracil (5-FU) and promoted cellular invasion. The secretome of CMS1 cells played a protective role for CMS4 cells against 5-FU treatment and mediated the transfer of metabolites between CMS1 and CMS4 cells.
CELL DEATH & DISEASE
(2023)
Review
Oncology
Ana Regina de Abreu, Ken Op de Beeck, Pierre Laurent-Puig, Valerie Taly, Leonor Benhaim
Summary: Currently available methods for detecting colorectal cancer (CRC) at an early stage and monitoring its progression during treatment are not always sensitive and specific enough. Circulating tumor DNA (ctDNA) has the potential to address this issue and personalize treatment for each patient at every stage of the disease. This review article provides an up-to-date overview of the clinical use and future directions of ctDNA in CRC management.
Article
Oncology
Maximiliano Gelli, Christophe Desterke, Mohamed Amine Bani, Valerie Boige, Charles Ferte, Peggy Dartigues, Bastien Job, Geraldine Perkins, Pierre Laurent-Puig, Diane Goere, Jacques R. R. Mathieu, Jerome Cartry, Michel Ducreux, Fanny Jaulin
Summary: This study aims to elucidate the primary tumor transcriptomic signatures associated with distinct metastatic routes in colorectal cancer (CRC). By analyzing the transcriptomic mRNA sequencing, gene set enrichment analyses and immunohistochemistry of primary tumor specimens, we identified a 61-gene signature that distinguishes between liver and peritoneal metastatic routes. The application of this transcriptomic signature could potentially identify new therapeutic targets for stage IV CRC and contribute to individualized follow-up programs in stage II-III CRC.
