Article
Biochemistry & Molecular Biology
Shujie Liu, Shuai Yan, Jie Zhu, Ruiqing Lu, Chujie Kang, Kang Tang, Jinfeng Zeng, Mingmei Ding, Zixiang Guo, Xianxin Lai, Yinan Jiang, Siqing Wu, Lihua Zhou, Litao Sun, Zhong-Wei Zhou
Summary: This study demonstrates the significant role of FTH1 in ferroptosis resistance in head and neck squamous cell carcinomas (HNSCCs) and provides clues for targeting HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jing Bi, Zhihui Wu, Xin Zhang, Taoling Zeng, Wanjun Dai, Ningyuan Qiu, Mingfeng Xu, Yikai Qiao, Lang Ke, Jiayi Zhao, Xinyu Cao, Qi Lin, Xiao Lei Chen, Liping Xie, Zhong Ouyang, Jujiang Guo, Liangkai Zheng, Chao Ma, Shiying Guo, Kangmei Chen, Wei Mo, Guo Fu, Tong-Jin Zhao, Hong-Rui Wang
Summary: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in TNBC progression. However, targeting EGFR using antibodies shows no significant benefits for TNBC patients. This study reveals that deficiency of TMEM25 allows EGFR monomer to activate STAT3 independent of ligand binding, promoting TNBC progression, and suggests TMEM25 as a potential targeted therapy for TNBC.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Tae-Gul Lee, Hye-Min Kang, Seo Yun Kim, Hye-Ryoun Kim, Cheol Hyeon Kim
Summary: Osimertinib, a third-generation EGFR TKI, is effective in treating EGFR-positive patients with T790 M resistance mutation. However, resistance to osimertinib develops and the mechanisms are not fully understood. In this study, osimertinib-resistant cells with upregulated phosphorylated ERK1/2 were established. KRAS amplification was observed in these cells and siRNA against KRAS reduced ERK1/2 activation and enhanced apoptosis induced by osimertinib. Combination treatment of osimertinib and RAF inhibitor LY3009120 showed remarkable synergistic anti-tumor activity. This could be a potential treatment option for osimertinib failure caused by KRAS amplification.
EXPERIMENTAL CELL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Won -Min Song, Pei-Ling Chia, Xianxiao Zhou, Martin Walsh, Jose Silva, Bin Zhang
Summary: Using single-nuclei RNA-seq, trajectory analysis was performed on chemoresistant tumor clones during neoadjuvant chemotherapy, revealing shared HER2-like tumor trajectories. By comparing transcriptomes, a consensus gene signature of TNBC chemoresistance was derived to predict FDA-approved drugs, such as afatinib. The study provides a dynamic model of chemoresistant tumor transcriptome and a computational framework for pharmacological intervention.
Review
Oncology
Gunnar Folprecht, Erika Martinelli, Thibault Mazard, Dominik P. Modest, Akihito Tsuji, Regina Esser, Chiara Cremolini, Alfredo Falcone
Summary: Triplet chemotherapy regimens in combination with anti-EGFR agents or bevacizumab are recommended standard treatments for unresectable mCRC. While the dosing schedule of FOLFOXIRI with bevacizumab is established, the optimal dosing with anti-EGFR agents is still unknown. Clinical trials have shown improved survival and response rates with FOLFOXIRI, alone or combined with bevacizumab, for mCRC patients, and promising results with anti-EGFR agents.
CANCER TREATMENT REVIEWS
(2022)
Review
Oncology
Yong Li, Xian Chen, Wenzhu Li, Yongsong Ye, Xiaohua Du, Shaodan Sun, Lirong Liu, Haibo Zhang
Summary: This study reported a successful case of treating mCRC patient with cetuximab in combination with fruquintinib after resistance to chemotherapy, showing good response. The mechanisms of this combination therapy and other clinical research on combined treatments were discussed, highlighting the potential benefits of combining small-molecule anti-vascular drugs with anti-EGFR in CRC treatment.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Alexander Rau, Nicole Janssen, Lennart Kuehl, Thomas Sell, Svetlana Kalmykova, Thomas E. Muerdter, Marc-H Dahlke, Christine Sers, Markus Morkel, Matthias Schwab, Roland E. Kontermann, Monilola A. Olayioye
Summary: The triple-HER receptor blockade using a newly developed bispecific antibody effectively inhibits HRG-induced HER receptor phosphorylation and reduces the risk of colon cancer relapse.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Guoqing Zhang, Beibei Yan, Yanan Guo, Hang Yang, Xiangnan Li, Jindong Li
Summary: Third-generation TKIs, such as osimertinib, almonertinib, and furmonertinib, are effective in overcoming drug resistance in EGFR mutations. However, resistance to these drugs can still occur, including a secondary mutation in the L718 residue of EGFR exon 18. Limited clinical experience exists for targeted therapy against this mutation. This study demonstrates that a combination of afatinib and cetuximab can overcome drug resistance caused by this mutation.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Qian Wu, Huan Wang, Suqin Zhang, Yifei Zeng, Wei Yang, Wenjun Pan, Guodai Hong, Wenbin Gao
Summary: This meta-analysis evaluated the efficacy and safety of triplet chemotherapy plus anti-EGFR target agents in potentially resectable metastatic colorectal cancer (mCRC) patients. The results showed that this treatment increased the objective response rate and the resection rate of colorectal liver metastasis. Adverse events were manageable. Further high-quality randomized controlled trials are needed for validation.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2022)
Article
Gastroenterology & Hepatology
M. Valery, B. Cervantesa, C. Smolenschi, A. Boileve, V. Boige, D. Malka, A. Hollebecque, M. Ducreux
Summary: This study analyzed the safety and efficacy of combining FOLFIRI and cetuximab as a treatment for metastatic squamous cell anal carcinoma (mSCAC) in patients who had previously failed on at least one line of treatment. The combination therapy showed a good disease control rate and manageable toxicity profile. Further prospective trials are needed to validate these results.
DIGESTIVE AND LIVER DISEASE
(2023)
Article
Oncology
Sanne ten Hoorn, Dirkje W. Sommeijer, Faye Elliott, David Fisher, Tim R. de Back, Anne Trinh, Lianne Koens, Tim Maughan, Jenny Seligmann, Matthew T. Seymour, Phil Quirke, Richard Adams, Susan D. Richman, Cornelis J. A. Punt, Louis Vermeulen
Summary: The study found that the efficacy of anti-EGFR therapy varies depending on different consensus molecular subtypes (CMSs) and primary tumor locations. The effectiveness of anti-EGFR therapy differs when using different chemotherapy backbones, showing favorable results in left-sided primary tumors with specific CMS subtypes. These findings suggest the potential for subtype-specific treatment strategies to optimize the use of anti-EGFR therapy.
BRITISH JOURNAL OF CANCER
(2021)
Article
Oncology
Lin Xia, Zaozao Zheng, Jun-Yi Liu, Yu-Jie Chen, Jiancheng Ding, Guo-Sheng Hu, Ya-Hong Hu, Suling Liu, Wen-Xin Luo, Ning-Shao Xia, Wen Liu
Summary: The study revealed that immunosuppressive genes induced by EGFR CAR T cells were sensitive to a CDK7 inhibitor THZ1, which can overcome resistance in TNBC tumors. Combination therapy with THZ1 and EGFR CAR T cells suppressed immune resistance, tumor growth, and metastasis in TNBC tumor models. This suggests that transcriptional modulation using epigenetic inhibitors could offer a potential avenue for treating TNBC in the clinic.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Yubo Wang, Rui Han, Mengxiao Zhu, Tingting He, Yong He
Summary: The efficacy of osimertinib is limited by the emergence of EGFR C797S. This study suggests that the combination target therapy of brigatinib and cetuximab may potentially be an effective treatment strategy for patients with acquired resistance mutations following osimertinib treatment.
FRONTIERS IN ONCOLOGY
(2022)
Review
Chemistry, Medicinal
Hannah Zaryouh, Ines De Pauw, Hasan Baysal, Marc Peeters, Jan Baptist Vermorken, Filip Lardon, An Wouters
Summary: Resistance to therapies targeting EGFR in HNSCC is a major challenge, with redundant activation of the PI3K/Akt pathway proposed as a key driver of resistance. Understanding the role of key proteins in this pathway is crucial for developing effective combination strategies. Studies on PI3K/Akt pathway inhibitors show promise in overcoming this resistance and improving clinical efficacy by co-targeting EGFR and PI3K/Akt pathways.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Chemistry, Medicinal
Chih-Hung Guo, Wen-Chin Li, Chia-Lin Peng, Pei-Chung Chen, Shih-Yu Lee, Simon Hsia
Summary: This study found that the combination of selenium/fish oil with gefitinib or erlotinib significantly reduced tumor volume and weight in lung cancer treatment, and also reduced metastasis. Furthermore, the combination treatment modulated multiple signaling pathways and immune checkpoint molecules, reduced angiogenesis, cancer stemness, epithelial to mesenchymal transitions, metastasis, and proliferation, and increased cell cycle arrest and apoptosis.
