Article
Oncology
Lorena Incorvaia, Daniele Fanale, Bruno Vincenzi, Ida De Luca, Tommaso Vincenzo Bartolotta, Roberto Cannella, Gianni Pantuso, Daniela Cabibi, Antonio Russo, Viviana Bazan, Giuseppe Badalamenti
Summary: The study suggests that the PFS of GIST patients to imatinib treatment may be related to different mutation types and locations of the KIT exon 11 gene, which have predictive value. Patients with deletions or insertions/deletions in codons 557/558 showed shorter PFS, while those with other types of mutations exhibited longer PFS.
Article
Biochemistry & Molecular Biology
Chi Yan, Chengzhi Zhao, Ke Yang, Hongyan Zhou, Limin Jing, Weixing Zhao, Wenguang Dou, Qingxin Xia, Jie Ma, Bing Wei, Yongjun Guo
Summary: This study identified two rare c-KIT gene mutations in GIST and melanoma patients, which play a novel role in resistance to imatinib, expanding the clinical research field.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Oncology
Andrea Napolitano, Khin Thway, Myles J. Smith, Paul H. Huang, Robin L. Jones
Summary: Exon 9-mutant GISTs represent a distinct subtype of GISTs that differ from other GIST subtypes, including the more common KIT exon 11-mutant GISTs. A better understanding of the molecular biology and clinical behavior of exon 9-mutant GISTs may help identify more improved treatment options.
Article
Biotechnology & Applied Microbiology
Douglas B. Snider, Greer K. Arthur, Guido H. Falduto, Ana Olivera, Lauren C. Ehrhardt-Humbert, Emmaline Smith, Cierra Smith, Dean D. Metcalfe, Glenn Cruse
Summary: This study developed an innovative approach using chemically stable exon skipping oligonucleotides (ESOs) to target KIT expression, which resulted in downregulation of KIT, inhibition of MC proliferation, and induction of apoptosis in neoplastic cells. In vivo administration of KIT targeting ESOs significantly inhibited tumor growth and organ infiltration, suggesting its potential as a therapeutic strategy for KIT-associated malignancies.
Article
Oncology
Lorena Incorvaia, Dario De Biase, Margherita Nannini, Elena Fumagalli, Bruno Vincenzi, Ida De Luca, Chiara Brando, Alessandro Perez, Maria A. Pantaleo, Silvia Gasperoni, Lorenzo D'Ambrosio, Giovanni Grignani, Thais Maloberti, Erika Pedone, Tancredi Didier Bazan Russo, Alessandro Mazzocca, Laura Algeri, Alessandra Dimino, Nadia Barraco, Roberta Serino, Valerio Gristina, Antonio Galvano, Viviana Bazan, Antonio Russo, Giuseppe Badalamenti
Summary: This study investigated the prognostic role of KIT or PDGFRA-VAF in GIST patients and found that higher VAF levels were independent predictors of poor prognosis and survival in localized GIST patients with KIT or PDGFRA mutations. This study is important for the prognostication and choice of adjuvant treatment in patients with gastrointestinal stromal tumors.
Article
Oncology
Shujing Li, Sien Zhao, Nianhai Liang, Shaoting Zhang, Liangying Zhang, Liangji Zhou, Anbu Liu, Xu Cao, Jinhai Tian, Yuanyuan Yu, Zhaoyang Fan, Kun Xiao, Ming Wang, Hui Zhao, Ru Bai, Jianmin Sun
Summary: In this study, the researchers investigated the role of SPRY4 in GISTs and its related mechanisms. They found that SPRY4 inhibits the expression and activation of KIT in GISTs, leading to decreased cell survival and proliferation. Additionally, SPRY4 enhances the inhibitory effect of Imatinib on primary KIT mutants, but has no effect on drug-resistant secondary KIT mutants.
Review
Oncology
Zhijun Zhang, Jian Shi, Tao Yang, Tongjun Liu, Kai Zhang
Summary: This review explores treatment options for desmoid tumors, finding that there is currently no standard therapy supported by data for high recurrence rates. Further research is needed to refine the efficacy and side effects of different modalities to provide a comprehensive treatment reference for clinicians.
Article
Biochemistry & Molecular Biology
Anbu Liu, Shaoting Zhang, Ming Wang, Liangying Zhang, Shidong Xu, Ahmad Nasimian, Shujing Li, Sien Zhao, Xu Cao, Jinhai Tian, Yuanyuan Yu, Zhaoyang Fan, Kun Xiao, Hui Zhao, Julhash U. Kazi, Lijun Ma, Jianmin Sun
Summary: This study demonstrates that DDR1/2 contribute to KIT activation and enhance resistance to imatinib in GISTs, providing a rationale for further exploration of DDR1/2 targeting in GIST treatment.
MOLECULAR CARCINOGENESIS
(2023)
Article
Oncology
Juan Liu, Jingjing Gao, Aoli Wang, Zongru Jiang, Shuang Qi, Ziping Qi, Feiyang Liu, Kailin Yu, Jiangyan Cao, Cheng Chen, Chen Hu, Hong Wu, Li Wang, Wenchao Wang, Qingsong Liu, Jing Liu
Summary: Drug resistance is a major challenge in the treatment of gastrointestinal stromal tumours (GISTs). A study has found that nintedanib can overcome resistance caused by mutations in the KIT gene and upregulation of fibroblast growth factor (FGF) activity. Nintedanib also showed inhibitory effects on cell proliferation and ERK phosphorylation in preclinical GIST models.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Joonha Kwon, Jun Hyeong Lee, Young Han Lee, Jeeyun Lee, Jin-Hee Ahn, Se Hyun Kim, Seung Hyun Kim, Tae Il Kim, Kum-Hee Yun, Young Suk Park, Jeong Eun Kim, Kyu Sang Lee, Jung Kyoon Choi, Hyo Song Kim
Summary: This study investigates the potential roles of NOTCH2 and HES1 in the clinical response to imatinib in patients with desmoid tumor. The results suggest a significant correlation between NOTCH2 mutations and clinical response to imatinib, and HES1 expression can differentiate responders from non-responders.
CANCER RESEARCH AND TREATMENT
(2022)
Article
Surgery
Zilin Zou, Guannan Ye, Saiqun Xu, Wei Liu, Weining Wang
Summary: This article describes a rare case of intra-abdominal aggressive fibromatosis in a young female with hyperemesis. Diagnosis of intra-abdominal aggressive fibromatosis was confirmed based on imaging and immunohistology findings. No local recurrence was observed during the 6-month follow-up after surgery.
FRONTIERS IN SURGERY
(2023)
Article
Multidisciplinary Sciences
Xiaoming Lu, Xiaoting Chen, Carmy Forney, Omer Donmez, Daniel Miller, Sreeja Parameswaran, Ted Hong, Yongbo Huang, Mario Pujato, Tareian Cazares, Emily R. Miraldi, John P. Ray, Carl G. de Boer, John B. Harley, Matthew T. Weirauch, Leah C. Kottyan
Summary: The study identified risk variants with allelic enhancer activity mediated through transcription factor binding through a combination of massively parallel reporter assay and genome-wide ChIP experiments.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Jodi M. Carter, Andres A. Maldonado, B. Matthew Howe, Scott Okuno, Robert J. Spinner
Summary: NMC-DTF often contains CTNNB1 p.S45 mutations, behaves aggressively, and requires adjuvant therapies for disease stabilization. Earlier adoption of systemic therapeutic strategies may be necessary for optimal disease management of NMC-DTF.
Review
Oncology
Newton A. C. S. Wong, Christel Garcia-Petit, Adam Dangoor, Nicola Andrew
Summary: It is well recognized that primary KIT or PDGFRA variant of gastrointestinal stromal tumor (GIST) can predict sensitivity to imatinib, but these data are currently scattered across various publications and have not been compiled as a single reference. A comprehensive literature search was conducted to establish a database that can optimize imatinib-based management of GIST patients. After excluding wild type GISTs and results of adjuvant therapy, data from 79 publications (spanning from August 2001 to March 2022) were extracted. These data on imatinib sensitivity were derived from in vitro studies, in silico analysis, or clinical patient response. The interpretation of these data had several limitations, but they demonstrated broad agreement of imatinib sensitivity among similar subtypes of KIT or PDGFRA variant.
Article
Biochemistry & Molecular Biology
Liliana Montella, Margaret Ottaviano, Vittorio Riccio, Fernanda Picozzi, Gaetano Facchini, Luigi Insabato, Mario Giuliano, Giovannella Palmieri
Summary: Langerhans cell histiocytosis is a rare disease with variable clinical presentation, and recent advances in understanding the role of mitogen-activated protein kinase signaling have led to increased use of targeted treatments. Imatinib, a tyrosine kinase inhibitor, has shown potential efficacy in refractory LCH cases, with positive results in controlling the disease noted in clinical studies.
Review
Oncology
Axel de Bernardi, Armelle Dufresne, Florence Mishellany, Jean-Yves Blay, Isabelle Ray-Coquard, Mehdi Brahmi
Summary: Solitary fibrous tumors (SFT) are rare tumors subdivided into three categories in the latest WHO classification. Current clinical guidelines for systemic treatment are inconsistent, with antiangiogenic therapy potentially being the best option. Recurrence rates can be high, with total en bloc resection as the standard treatment for localized SFT and limited efficacy of conventional chemotherapy for advanced disease.
Article
Oncology
Anastasios Kyriazoglou, Pieter Jespers, Vincent Vandecavaye, Olivier Mir, Bernd Kasper, Zsuzsanna Papai, Jean-Yves Blay, Antoine Italiano, Facundo Zaffaroni, Saskia Litiere, Axelle Nzokirantevye, Patrick Schoffski
Summary: This study evaluated the treatment response in gastrointestinal stromal tumors (GISTs) and compared different assessment methods. The results showed that cabozantinib is active in GIST patients who have been treated with imatinib and sunitinib. Furthermore, the study demonstrated the limitations of the traditional RECIST assessment method in capturing the response to tyrosine kinase inhibitors (TKIs) in GIST patients, emphasizing the importance of including density changes in the evaluation.
Article
Oncology
Andy Karabajakian, Isabelle Ray-Coquard, Jean-Yves Blay
Summary: Kaposi's sarcoma has multiple forms, with the HIV-related form being the most aggressive and involving different areas. Kaposi's sarcoma-associated herpes virus is the underlying cause of the disease, affecting host cell proliferation and angiogenesis, and also impacting immune response.
Article
Oncology
Christian Rothermundt, Dimosthenis Andreou, Jean-Yves Blay, Thomas Brodowicz, Ingrid M. E. Desar, Palma Dileo, Hans Gelderblom, Rick Haas, Jens Jakob, Robin L. Jones, Ian Judson, Wolfgang G. Kunz, Berndadette Liegl-Atzwanger, Lars H. Lindner, Christina Messiou, Aisha B. Miah, Peter Reichardt, Joanna Szkandera, Winette T. A. van der Graaf, Winan J. van Houdt, Eva Wardelmann, Silvia Hofer
Summary: This article summarizes the multiple issues and controversies in the diagnosis, treatment, and follow-up of soft tissue sarcoma (STS). It also identifies scientific questions that need to be addressed for improved patient management and outcomes. The study used a modified Delphi process and a voting survey to gather experts' opinions and determine areas of consensus and controversy. The article proposes future scientific questions, clinical trials, quality assurance, and actions by stakeholders to enhance the management and research in STS.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Philip Heesen, Gabriela Studer, Beata Bode, Hubi Windegger, Benjamin Staeheli, Paul Aliu, Javier Martin-Broto, Alessandro Gronchi, Jean-Yves Blay, Axel Le Cesne, Bruno Fuchs
Summary: This article presents a comprehensive analysis of quality indicators for sarcoma care and introduces a novel interoperable digital platform that gathers information from physicians and patients consecutively and instantly. The platform provides evidence of care quality by analyzing real-time world information, enabling predictive modeling and value-based health care. The lack of global data harmonization and quality standards, as well as discipline, institution, and network fragmentation, hinder the progress in sarcoma care. To improve quality, a common definition of quality indicators and the assessment of longitudinal real-time data are required. An international advisory board defined six categories of quality indicators, which were programmed into the digital platform for analysis and visualization. Standardized quality indicators and their real-time assessment are critical to improving the quality of sarcoma care.
Article
Oncology
Elodie Darbo, Gaelle Perot, Lucie Darmusey, Sophie Le Guellec, Laura Leroy, Laetitia Gaston, Nelly Desplat, Noemie Thebault, Candice Merle, Philippe Rochaix, Thibaud Valentin, Gwenael Ferron, Christine Chevreau, Binh Bui, Eberhard Stoeckle, Dominique Ranchere-Vince, Pierre Meeus, Philippe Terrier, Sophie Piperno-Neumann, Francoise Collin, Gonzague De Pinieux, Florence Duffaud, Jean-Michel Coindre, Jean-Yves Blay, Frederic Chibon
Summary: Leiomyosarcomas are aggressive diseases mainly treated by surgical resection with or without conventional chemotherapy. Two specifically deregulated pathways (MYOCD/SRF and E2F1/RB1) were identified in a subgroup of well-differentiated vascular smooth muscle cell-derived leiomyosarcomas. Targeting the MYOCD/SRF pathway has the potential to be a therapeutic target for leiomyosarcoma.
Article
Biochemistry & Molecular Biology
Vivek Subbiah, Robert J. Kreitman, Zev A. Wainberg, Anas Gazzah, Ulrik Lassen, Alexander Stein, Patrick Y. Wen, Sascha Dietrich, Maja J. A. de Jonge, Jean-Yves Blay, Antoine Italiano, Kan Yonemori, Daniel C. Cho, Filip Y. F. L. de Vos, Philippe Moreau, Elena Elez Fernandez, Jan H. M. Schellens, Christoph C. Zielinski, Suman Redhu, Aislyn Boran, Vanessa Q. Passos, Palanichamy Ilankumaran, Yung-Jue Bang
Summary: This study is a phase 2 basket trial evaluating the efficacy and safety of dabrafenib plus trametinib in patients with BRAFV600E-mutated advanced rare cancers. The overall response rates in different tumor types ranged from 56% to 89%. Secondary endpoints included duration of response, progression-free survival, overall survival, and safety.
Article
Oncology
Benoit Allignet, Paul Pou, Floriane Izarn, Isabelle Ray-Coquard, Jean-Yves Blay, Armelle Dufresne, Mehdi Brahmi, Amine Bouhamama, Pierre Meeus, Gualter Vaz, Francois Gouin, Alexandra Meurgey, Marie Karanian, Coralie Moncharmont, Waisse Waissi, Marie-Pierre Sunyach
Summary: The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy in patients with soft-tissue sarcoma re-excised after unplanned tumor resection. The results showed that adjuvant radiotherapy was associated with reduced local failure and longer local recurrence-free survival. Age and tumor grade were independent predictors of the effectiveness of adjuvant radiotherapy. Overall, adjuvant radiotherapy was safe and beneficial for patients with soft-tissue sarcoma re-excised after unplanned tumor resection.
Article
Oncology
Florence Duffaud, Jean-Yves Blay, Axel Le Cesne, Christine Chevreau, Pascaline Boudou-Rouquette, Elsa Kalbacher, Nicolas Penel, Christophe Perrin, Valerie Laurence, Emmanuelle Bompas, Esma Saada-Bouzid, Corinne Delcambre, Francois Bertucci, Mathilde Cancel, Camille Schiffler, Laure Monard, Corinne Bouvier, Vincent Vidal, Nathalie Gaspar, Sylvie Chabaud
Summary: Although the primary endpoint was not met statistically in this randomised cohort, there is evidence to suggest that regorafenib might modestly delay tumour progression in relapsed ES after failure of prior chemotherapy.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Hans Gelderblom, Robin L. Jones, Jean-Yves Blay, Suzanne George, Margaret von Mehren, John R. Zalcberg, Yoon-Koo Kang, Albiruni Abdul Razak, Jonathan Trent, Steven Attia, Axel Le Cesne, Brittany L. Siontis, David Goldstein, Kjetil Boye, Cesar Sanchez, Neeltje Steeghs, Piotr Rutkowski, Mihaela Druta, Cesar Serrano, Neeta Somaiah, Ping Chi, Brooke Harrow, Claus Becker, William Reichmann, Matthew L. Sherman, Rodrigo Ruiz-Soto, Michael C. Heinrich, INTRIGUE Investigators
Summary: In the INTRIGUE trial, there was no significant difference in progression-free survival between ripretinib and sunitinib for advanced gastrointestinal stromal tumour (GIST) patients. The study compared the impact of these treatments on health-related quality of life (HRQoL) and found that patients receiving ripretinib had better HRQoL during the dosing period compared to patients receiving sunitinib.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Iseulys Richert, Paul Berchard, Lhorra Abbes, Alexey Novikov, Kamel Chettab, Alexandra Vandermoeten, Charles Dumontet, Marie Karanian, Jerome Kerzerho, Martine Caroff, Jean-Yves Blay, Aurelie Dutour
Summary: This study demonstrates the potent antitumor effect of chemically detoxified TLR4 agonist Lipo-MP-LPS in the treatment of osteosarcoma. Lipo-MP-LPS controls tumor growth by altering the immune microenvironment and reprogramming macrophages, providing a new immunomodulatory approach for highly resistant tumors like osteosarcoma.
Article
Oncology
Maud Toulmonde, Derek Dinart, Mehdi Brahmi, Benjamin Verret, Myriam Jean-Denis, Francoise Ducimetiere, Gregoire Desolneux, Pierre Meeus, Jean Palussiere, Xavier Buy, Amine Bouhamama, Pauline Gillon, Armelle Dufresne, Clemence Henon, Francois Le Loarer, Marie Karanian, Carine Ngo, Simone Mathoulin-Pelissier, Carine Bellera, Axel Le Cesne, Jean Yves Blay, Antoine Italiano
Summary: This study assesses the evolution of treatment strategies for patients with metastatic gastrointestinal stromal tumors (GIST) in three French expert centers over 30 years. It highlights the importance of clinical trials and locoregional procedures in improving survival for GIST patients and suggests early referral to expert centers for access to innovative treatments. The study also shows that there is no significant difference in the effectiveness of different tyrosine kinase inhibitors (TKI) in later lines of treatment since the introduction of imatinib.
Article
Oncology
Olivier Tredan, Maud Toulmonde, Christophe Le Tourneau, Laure Montane, Antoine Italiano, Isabelle Ray-Coquard, Christelle de la Fouchardiere, Francois Bertucci, Anthony Goncalves, Carlos Gomez-Roca, Benoit You, Valery Attignon, Sandrine Boyault, Philippe A. Cassier, Armelle Dufresne, Severine Tabone-Eglinger, Alain Viari, Emilie Sohier, Maud Kamal, Gwenael Garin, Jean-Yves Blay, David Perol
Summary: Using a randomized discontinuation design, sorafenib was tested on patients with advanced/metastatic solid tumors harboring sorafenib-targeted genes. Continuing sorafenib when stable disease is achieved improves progression-free rate compared to interruption. Sorafenib has tumor-agnostic efficacy in patients with tumors harboring genomic alterations in PDGFRA/B, VEGF-Rs, Flt-3, KIT, FGFR1 or the RAF/MEK/ERK pathway.
Article
Oncology
Xiaolan Feng, Laurie Tonon, Haocheng Li, Elodie Darbo, Erin Pleasance, Nicolas Macagno, Armelle Dufresne, Mehdi Brahmi, Julien Bollard, Francoise Ducimetiere, Marie Karanian, Alexandra Meurgey, Gaelle Perot, Thibaud Valentin, Frederic Chibon, Jean-Yves Blay
Summary: This study is the first comprehensive transcriptomic profiling analysis focused on the tumor immune microenvironment (TIME) in leiomyosarcoma (LMS). The study identified a subset of LMS patients with an active immune microenvironment, which is associated with validated immune signatures observed in other cancers. The study supports the further development of immune biomarkers to select the right LMS patients for immune checkpoint inhibitors (ICIs) in clinical trials.
Article
Oncology
J. Y. Blay, C. Cropet, S. Mansard, Y. Loriot, C. De La Fouchardiere, J. Haroche, D. Topart, D. Tougeron, B. You, A. Italiano, V. Le Brun-Ly, J. M. Ferrero, N. Penel, M. Fabbro, X. Troussard, D. Malka, I. Ray-Coquard, S. Leboulleux, A. Flechon, E. Maubec, J. Charles, S. Dalle, S. Taieb, G. C. T. E. Garcia, A. M. Mandache, N. Colignon, M. Gavrel, F. Nowak, N. Hoog Labouret, C. Mahier Ait Oukhatar, C. Gomez-Roca
Summary: Vemurafenib demonstrates efficacy and prolonged PFS in advanced tumors with BRAF mutations other than melanoma and NSCLC. This therapy is effective for various tumor types including HCL, ECD, ovarian carcinoma, gliomas, ganglioglioma, and sarcomas.
