Article
Cell Biology
Po-Hsuan Su, Rui-Lan Huang, Hung-Cheng Lai, Lin-Yu Chen, Yu-Chun Weng, Chih-Chien Wang, Chia-Chun Wu
Summary: NKX6-1 expression is associated with poor prognosis and malignant potential in LMS, enhancing tumor cell aggressiveness in vitro and promoting tumor growth in vivo. Overexpression and knockdown of NKX6-1 affect stem cell transcription factors and signaling pathways, including the NOTCH and Sonic hedgehog pathways. Inhibition of the SHH pathway may be a potential therapeutic strategy for LMS patients with high expression of NKX6-1.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Cell Biology
Wanshuang Cao, Yuan Li, Hongliang Sun, Chenying Yang, Jianyun Zhu, Chunfeng Xie, Xiaoting Li, Jieshu Wu, Shanshan Geng, Lu Wang, Liangfei Sun, Guozhu Geng, Hongyu Han, Caiyun Zhong
Summary: The study found that apatinib effectively suppressed GCSC traits, including inhibiting tumorsphere formation and cell proliferation, reducing GCSC markers expression and CD133(+) cell number, and inducing apoptosis. Additionally, apatinib downregulated the SHH pathway activation, which was crucial for inhibiting GCSCs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Oncology
Jiabao Hou, Hongle Li, Shuxiang Ma, Zhen He, Sen Yang, Lidan Hao, Hanqiong Zhou, Zhe Zhang, Jing Han, Li Wang, Qiming Wang
Summary: Platinum-based chemotherapy used to be the first choice for lung cancer, but EGFR tyrosine kinase inhibitors (TKIs) have become preferred treatment for NSCLC patients with EGFR gene mutations. However, patients with EGFR exon 20 insertion (ex20ins) mutations have poor prognosis and are insensitive to EGFR-TKIs. Recent clinical research has focused on developing therapies specifically targeting ex20ins mutations.
BIOMARKER RESEARCH
(2022)
Review
Oncology
Qi Zhu, Mingyun Jiang, Wenfei Li, Shuangli Sun, Jisheng Li, Justin Stebbing, Xiaodong Liang, Ling Peng
Summary: This study reported a case of a rare EGFR V786M mutation, which showed sensitivity to EGFR-TKIs and induced conformational changes. These findings provide evidence for further investigation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Surgery
Ronan J. Kelly, Amir M. Ansari, Tomoharu Miyashita, Marianna Zahurak, Frank Lay, A. Karim Ahmed, Louis J. Born, Maryam K. Pezhouh, Kevan J. Salimian, Christopher Ng, Aerielle E. Matsangos, Anne-Heloise Stricker-Krongrad, Ken-ichi Mukaisho, Guy P. Marti, Christine H. Chung, Marcia I. Canto, Michelle A. Rudek, Stephen J. Meltzer, John W. Harmon
Summary: Itraconazole significantly reduces the development of esophageal adenocarcinoma and SHH expression in a preclinical animal model of Barrett's Metaplasia. In humans, BE tissue expresses higher levels of SHH, Indian Hedgehog, and bone morphogenic protein compared to normal squamous esophageal epithelium.
Article
Chemistry, Medicinal
Christopher Lawson, Thowaiba Babikr Ahmed Alta, Georgia Moschou, Vasiliki Skamnaki, Theodora G. A. Solovou, Caroline Topham, Joseph Hayes, Timothy J. Snape
Summary: Medulloblastoma is a highly aggressive and heterogeneous tumor that accounts for 15-20% of childhood brain tumors. In this study, potent in vitro anticancer activity against medulloblastoma cell lines was achieved using first-generation compounds, leading to the development of second-generation compounds with up to sixty times the activity, providing promising new leads for further research.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kento Takaya, Noriko Aramaki-Hattori, Shigeki Sakai, Keisuke Okabe, Kazuo Kishi
Summary: The expression of sonic hedgehog (Shh) is involved in the regeneration of texture during wound healing, especially in epidermal keratinocyte migration and division.
Article
Oncology
Takashi Ito, Hiromi Nagashima, Masachika Akiyama, Yu Utsumi, Hideomi Sato, Shinji Chiba, Mayu Sugai, Kenji Ube, Yoshiaki Mori, Kana Watanabe, Tatsuro Fukuhara, Makoto Maemondo
Summary: EGFR-mutated NSCLC patients with L858R mutation are more likely to respond well to ICI treatment. The occurrence of T790M resistance mutation before ICI treatment did not differ significantly between different response groups. Patients with shorter duration of EGFR-TKI pretreatment are more likely to respond well to ICI treatment.
Article
Oncology
Paul Takam Kamga, Aurelie Swalduz, Adrien Costantini, Catherine Julie, Jean-Francois Emile, Maurice Perol, Virginie Avrillon, Sandra Ortiz-Cuaran, Pierre de Saintigny, Etienne Giroux Leprieur
Summary: The study found that high levels of plasma Shh are associated with resistance to EGFR TKI therapy and poor prognosis in EGFRm NSCLC patients, suggesting that Shh levels could serve as both prognostic and resistance biomarkers.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Rilan Bai, Xiao Chen, Wei Song, Huimin Tian, Jiuwei Cui
Summary: EGFR exon 20 insertion (EGFR ex20ins) mutations account for a certain percentage of EGFR-mutated tumors, often associated with drug resistance and poor survival outcomes. Recent advancements in treatment options have accelerated the development of new drugs and rational combination therapies, aiming to improve the prognosis of this rare mutant population.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Oncology
Camille Mehlman, Paul Takam Kamga, Adrien Costantini, Catherine Julie, Coraline Dumenil, Jennifer Dumoulin, Julia Ouaknine, Violaine Giraud, Thierry Chinet, Jean-Francois Emile, Etienne Giroux Leprieur
Summary: The activation of the Hedgehog (Hh) and Wingless-type (Wnt) pathways was found to be associated with resistance to immune checkpoint inhibitors (ICIs) in NSCLC patients. Baseline Hh activation and increased Wnt1 levels during ICI treatment were both associated with poor outcomes in this study.
Article
Oncology
Hualin Chen, Donghong Yang, Yongcun Wang, Hua Tao, Yiping Luo, Aibing Wu, Shujun Li, Zhixiong Yang, Ming Chen
Summary: The Hedgehog pathway plays a crucial role in EGFR TKI resistance and EMT induction in NSCLC, and its inhibition can reverse TKI resistance. The combination of Hedgehog pathway inhibitors with TKIs can enhance sensitivity to chemotherapy.
Article
Oncology
Aram Ko, Mohammad Hasanain, Young Taek Oh, Fulvio D'Angelo, Danika Sommer, Brulinda Frangaj, Suzanne Tran, Franck Bielle, Bianca Pollo, Rosina Paterra, Karima Mokhtari, Rajesh Kumar Soni, Matthieu Peyre, Marica Eoli, Laura Papi, Michel Kalamarides, Marc Sanson, Antonio Iavarone, Anna Lasorella
Summary: LZTR1 is a substrate-specific adaptor of a CUL3-dependent ubiquitin ligase frequently mutated in cancer. The study identified EGFR and AXL as LZTR1 substrates targeted for degradation, and found that LZTR1 mutations result in the accumulation and deregulated signaling of EGFR and AXL. The study also revealed vulnerabilities of LZTR1-mutant tumors to inhibition of EGFR and AXL, providing precision targeting for patients with LZTR1-mutant cancer.
Article
Pharmacology & Pharmacy
Jeyalakshmi Kandhavelu, Kumar Subramanian, Vivash Naidoo, Giulia Sebastianelli, Phuong Doan, Saravanan Konda Mani, Hande Yapislar, Ebru Haciosmanoglu, Leman Arslan, Samed Ozer, Ramesh Thiyagarajan, Nuno R. Candeias, Clement Penny, Meenakshisundaram Kandhavelu, Akshaya Murugesan
Summary: This study identified a potent EGFR inhibitor called HNPMI, which modulates the apoptosis and oncogenesis processes in CRC cell lines by regulating proteins such as BCL-2/BAX and p53. The results indicate that HNPMI has the potential to be a therapeutic agent for the treatment of CRC.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Oncology
Nathaniel Wiest, Umair Majeed, Karan Seegobin, Yujie Zhao, Yanyan Lou, Rami Manochakian
Summary: In the past decade, the treatment of advanced EGFRm NSCLC has seen rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. Newer-generation TKIs have shown unparalleled survival benefit for EGFRm NSCLC patients. However, the application of ICI therapy to these patients is controversial, with early studies showing inferiority to other treatment methods.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Adrien Costantini, Paul Takam Kamga, Catherine Julie, Alexandre Corjon, Coraline Dumenil, Jennifer Dumoulin, Julia Ouaknine, Violaine Giraud, Thierry Chinet, Martin Rottman, Jean-Francois Emile, Etienne Giroux Leprieur
Summary: This study identified an association between ICIs efficacy and three cytokines, as well as potential biomarkers for predicting immune-related toxicity in advanced NSCLC. The results suggest the potential role of new plasma biomarkers in predicting outcomes and adverse events in NSCLC patients treated with ICIs.
Article
Oncology
Camille Mehlman, Paul Takam Kamga, Adrien Costantini, Catherine Julie, Coraline Dumenil, Jennifer Dumoulin, Julia Ouaknine, Violaine Giraud, Thierry Chinet, Jean-Francois Emile, Etienne Giroux Leprieur
Summary: The activation of the Hedgehog (Hh) and Wingless-type (Wnt) pathways was found to be associated with resistance to immune checkpoint inhibitors (ICIs) in NSCLC patients. Baseline Hh activation and increased Wnt1 levels during ICI treatment were both associated with poor outcomes in this study.
Editorial Material
Oncology
Umberto Malapelle, Etienne Giroux Leprieur, Paul Takam Kamga, Marius Tresor Chiasseu, Christian Rolfo
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Alexis B. Cortot, Anne Madroszyk, Etienne Giroux-Leprieur, Olivier Molinier, Elisabeth Quoix, Henri Berard, Josiane Otto, Isabelle Rault, Denis Moro-Sibilot, Judith Raimbourg, Elodie Amour, Franck Morin, Jose Hureaux, Lionel Moreau, Didier Debieuvre, Hugues Morel, Aldo Renault, Eric Pichon, Benjamin Huret, Sandrine Charpentier, Marc G. Denis, Jacques Cadranel
Summary: The addition of cetuximab to afatinib in the treatment of treatment-naive advanced EGFR-mutant NSCLC did not show any significant improvement in efficacy, suggesting that further investigation into this combination therapy may not be warranted.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Romain-David Seban, Jean-Baptiste Assie, Etienne Giroux-Leprieur, Marie-Ange Massiani, Gerald Bonardel, Christos Chouaid, Nicolas Deleval, Capucine Richard, Laura Mezquita, Nicolas Girard, Laurence Champion
Summary: The study revealed that high dNLR, high SII, and high SLR were independent prognostic factors in NSCLC patients treated with immunotherapy, while high BLR and high dNLR were associated with shorter progression-free survival and overall survival in patients treated with chemotherapy. BLR showed moderate correlations with most blood-based inflammatory indices, while SLR was only associated with CRP levels.
Article
Respiratory System
Armin Frille, Adrien Costantini, Katherina B. Sreter
Article
Oncology
Geoffroy Bilger, Nicolas Girard, Helene Doubre, Matteo Giaj Levra, Etienne Giroux-Leprieur, Frederique Giraud, Chantal Decroisette, Matthieu Carton, Marie Ange Massiani
Summary: This study analyzed the characteristics of patients with controlled disease who discontinued ICI treatment after at least 18 months. The results showed that 50% of patients stopped ICI treatment, mainly due to prescriber choice or toxicity. After a median follow-up of 21 months from treatment discontinuation, 33% of patients experienced tumor progression.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Samy Chelabi, Xavier Mignard, Karen Leroy, Isabelle Monnet, Solenn Brosseau, Nathalie Theou-Anton, Marie-Ange Massiani, Sylvie Friard, Boris Duchemann, Elizabeth Fabre, Etienne Giroux-Leprieur, Jacques Cadranel, Marie Wislez
Summary: EGFR exon 20 insertions are rare genetic alterations in NSCLC that are resistant to classic EGFR TKIs, showing poor response to treatment and shorter overall survival compared to classic EGFR mutation patients.
Article
Oncology
Paul Takam Kamga, Aurelie Swalduz, Adrien Costantini, Catherine Julie, Jean-Francois Emile, Maurice Perol, Virginie Avrillon, Sandra Ortiz-Cuaran, Pierre de Saintigny, Etienne Giroux Leprieur
Summary: The study found that high levels of plasma Shh are associated with resistance to EGFR TKI therapy and poor prognosis in EGFRm NSCLC patients, suggesting that Shh levels could serve as both prognostic and resistance biomarkers.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Pierre Magdelaine, Adrien Costantini, Lucie Fabre, Etienne Giroux-Leprieur
Summary: This case report describes a 73-year-old female patient with cT4N0M1a lung adenocarcinoma and KRAS G12C mutation, PDL1 < 1%, who was treated with gemcitabine as a fourth-line therapy after progressing on nivolumab. The patient developed acute generalized exanthematous pustulosis after one infusion of gemcitabine, but showed a remarkable tumor response on all cancer localizations after two months of follow-up. This case emphasizes that immune-stimulation can lead to tumor response in patients who were previously refractory to all antitumor treatments.
Article
Oncology
Remy Ezzedine, Anthony Canellas, Charles Naltet, Marie Wislez, Reza Azarian, Andrei Seferian, Etienne Giroux Leprieur
Summary: Chemoimmunotherapy has shown superiority in the real-life treatment of advanced small cell lung cancer, especially in patients with brain and liver metastases. However, it is not beneficial for patients aged 70 or older with impaired performance status.
Article
Oncology
Lahcene Belaidi, Pascal Wang, Kevin Quintin, Catherine Durdux, Etienne Giroux-Leprieur, Philippe Giraud
Summary: Stereotactic radiotherapy (SRT) is increasingly important in the management of metastatic non-small-cell lung cancer (mNSCLC). However, the optimal timing of SRT in relation to systemic treatment remains unclear. This study compared the survival outcomes of patients who received early or late SRT in relation to first-line systemic therapy. The results showed that delaying SRT treatment may be less necessary when an immune checkpoint inhibitor is administered in mNSCLC.
