Review
Pharmacology & Pharmacy
Jazlyn P. Borges, Katrina Mekhail, Gregory D. Fairn, Costin N. Antonescu, Benjamin E. Steinberg
Summary: Chronic pain is a major public health issue that is often resistant to conventional analgesics. Recent studies have implicated the epidermal growth factor receptor (EGFR) signaling pathway in chronic pain, suggesting potential therapeutic targets for this devastating condition.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Paolo Zucchiatti, Giovanni Birarda, Andrea Cerea, Marta S. Semrau, Aliaksandr Hubarevich, Paola Storici, Francesco De Angelis, Andrea Toma, Lisa Vaccari
Summary: This study demonstrates the potential of SEIRA microscopy in detecting subtle secondary structure modifications associated with the binding of Lapatinib to EGFR. By optimizing techniques and data analysis, the researchers successfully identified secondary structure modifications in EGFR related to a few amino acids.
Review
Biochemistry & Molecular Biology
Chao Wang, Yujing Zhang, Tingting Zhang, Jiazhen Xu, Saisai Yan, Bing Liang, Dongming Xing
Summary: Overexpression of EGFR has been linked to various cancers, and drug resistance caused by EGFR mutations is a significant challenge. EGFR dual-target inhibitors show promise in overcoming drug resistance and have higher efficacy compared to single-target inhibitors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Oncology
Ying-Yi Chen, Kuan-Hsun Lin, Yen-Shou Kuo, Yuan-Ming Tsai, Hsu-Kai Huang, Tsai-Wang Huang
Summary: This study investigated the impact of EGFR-TKI in patients with advanced lung adenocarcinoma treated with various therapeutic strategies. The results showed that TKI with lung cancer salvage surgery is the best therapeutic strategy, leading to significantly longer overall survival and extended duration of TKI usage.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Thushara W. Madanayake, Eric A. Welsh, Lancia N. F. Darville, John M. Koomen, Charles E. Chalfant, Eric B. Haura, Timothy J. Robinson
Summary: We have developed a novel method to inhibit EGFR signaling using custom ASOs to induce exon skipping and drive the expression of dominant negative mRNA isoforms of EGFR. Our in vivo experiments showed that ASOs were highly effective in inhibiting colony formation, cell viability, and migration in EGFR mutant NSCLC. Importantly, ASOs maintained their efficacy in erlotinib-resistant subclones and wild-type EGFR overexpressing models, where erlotinib had no significant effect. By directly targeting the EGFR kinase domain, ASOs resulted in maximal inhibition of EGFR phosphorylation and downstream signaling in both EGFR mutant and erlotinib-resistant cells. Furthermore, our study confirmed the EGFR-specific therapeutic mechanism of ASOs in EGFR-independent NSCLC models. Further investigation of the synergy between ASOs and existing tyrosine kinase inhibitors could provide new clinical models to improve EGFR-targeted therapies for NSCLC patients, both mutant and wild-type.
NUCLEIC ACID THERAPEUTICS
(2022)
Article
Oncology
Sojung Park, Sung Yong Lee, Dojin Kim, Yun Su Sim, Jeong-Seon Ryu, Juwhan Choi, Su Hwan Lee, Yon Ju Ryu, Jin Hwa Lee, Jung Hyun Chang
Summary: This study investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations and evaluated the efficacy of afatinib, erlotinib, and gefitinib according to mutation type. E19del and L858R mutations were associated with superior progression-free survival and overall survival compared to uncommon mutations. Afatinib showed significantly longer progression-free survival across all EGFR mutation types.
Article
Biochemistry & Molecular Biology
Yumiko Tahira, Katsuya Sakai, Hiroki Sato, Ryu Imamura, Kunio Matsumoto
Summary: The researchers found that the residues N127, V140, and K144 at the NK1 dimer interface play important roles in Met activation by HGF. Mutant NK1 proteins with alanine replacements at these residues lost their ability to activate Met, while mutant HGF proteins with the same replacements retained their activity, suggesting a distinction in the structural basis for NK1-dependent Met dimer formation and HGF-dependent Met activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Yongjian Huang, Jana Ognjenovic, Deepti Karandur, Kate Miller, Alan Merk, Sriram Subramaniam, John Kuriyan
Summary: Research has shown that the EGFR receptor can adopt different conformations of the extracellular module when binding to different ligands, with implications for intracellular signaling pathways.
Article
Pharmacology & Pharmacy
Yusuke Masuo, Ken-ichi Fujita, Kazuhiro Shimada, Noriho Iida, Tomohiko Wakayama, Yukio Kato, Aya Hasan Alshammari
Summary: This study explains the occurrence of hand-foot skin reaction (HFSR) in patients treated with tyrosine kinase inhibitors (TKIs) by examining keratinocyte toxicity and VEGFR-2 inhibition.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Ning Liu, Lingnan Zheng, Min Yu, Shuang Zhang
Summary: This case report describes a patient with EGFR-mutant lung adenocarcinoma coexisting with pulmonary tuberculosis. The patient was initially diagnosed with pneumonia-like pulmonary adenocarcinoma and later confirmed to have active tuberculosis. The patient received a combination therapy of gefitinib and anti-TB treatment, leading to stable disease status and survival.
Article
Cell Biology
Faten Abdelli, Karim Jellali, Estefania Anguita, Maria Gonzalez-Munoz, Eduardo Villalobo, Ivan Madronal, Juan Alcalde, Mamdouh Ben Ali, Jihene Elloumi-Mseddi, Ikram Jemel, Francesc Tebar, Carlos Enrich, Sami Aifa, Antonio Villalobo
Summary: The study shows that EGFR with CaM-BD and CaM-LD domains affects the receptor's TK activity. Different EGFR mutants exhibit varying abilities to bind EGF, localize to the plasma membrane, and undergo ligand-dependent internalization.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Ryo Miyata, Masatsugu Hamaji, Atsushi Kawaguchi, Yumeta Shimazu, Masaki Ikeda, Masashi Ishikawa, Hidenao Kayawake, Toshi Menju, Masashi Kobayashi, Norihito Okumura, Yasuto Sakaguchi, Makoto Sonobe, Akira Matsumoto, Tsuyoshi Shoji, Hiromichi Katakura, Ryota Sumitomo, Cheng-Long Huang, Mamoru Takahashi, Akihiro Aoyama, Yusuke Muranishi, Tomoya Kono, Ryo Miyahara, Naoki Date, Takuji Fujinaga, Ei Miyamoto, Tatsuo Nakagawa, Takahisa Fukada, Hiroaki Sakai, Hiroshi Date
Summary: This study analyzed the long-term survival outcomes and prognostic factors of patients with postoperative recurrent EGFR-mutated lung adenocarcinoma who received EGFR-TKIs as first-line treatment. The study found that first-line EGFR-TKI treatment was generally associated with favorable survival outcomes. EGFR ex 21 L858R mutation may be an important prognostic factor for shorter progression-free survival (PFS).
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
(2022)
Article
Oncology
Lijuan Zhang, Meng Tian, Jiamao Lin, Jianbo Zhang, Haiyong Wang, Zhenxiang Li
Summary: The interaction between ER beta 1 and ER beta 5 in lung adenocarcinoma affects non-genomic signaling and resistance to EGFR TKIs. Cytoplasmic ER beta 1 may contribute to EGFR TKI resistance, and PC9/ER beta 1/5 cells show higher resistance to gefitinib.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Yu-Jin Wang, Qing-Wen Wang, Dong-Hu Yu, Cong-Kuan Song, Zi-Xin Guo, Xiao-Ping Liu, Chen Chen, Jie Yao, Ai-Fen Wang, Wei-Dong Hu
Summary: The correlation between Osteopontin (OPN) and EGFR affects the sensitivity of lung adenocarcinoma (LUAD) cells to the first-generation TKI gefitinib, suggesting OPN as a potential target for molecular therapy.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Oncology
Qing Chang, Huiping Qiang, Jialin Qian, Yuqiong Lei, Jiahuan Lu, Hui Feng, Yiming Zhao, Baohui Han, Yanwei Zhang, Tianqing Chu
Summary: For advanced Chinese female lung SCC patients with EGFR positive mutations, targeted therapy could confer longer progression-free survival (PFS) and overall survival (OS) than chemotherapy, but the survival was similar with patients who were negative EGFR mutations.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Luiza Moore, Daniel Leongamornlert, Tim H. H. Coorens, Mathijs A. Sanders, Peter Ellis, Stefan C. Dentro, Kevin J. Dawson, Tim Butler, Raheleh Rahbari, Thomas J. Mitchell, Francesco Maura, Jyoti Nangalia, Patrick S. Tarpey, Simon F. Brunner, Henry Lee-Six, Yvette Hooks, Sarah Moody, Krishnaa T. Mahbubani, Mercedes Jimenez-Linan, Jan J. Brosens, Christine A. Iacobuzio-Donahue, Inigo Martincorena, Kourosh Saeb-Parsy, Peter J. Campbell, Michael R. Stratton
Article
Oncology
Hitomi Sakamoto, Marc A. Attiyeh, Jeffrey M. Gerold, Alvin P. Makohon-Moore, Akimasa Hayashi, Jungeui Hong, Rajya Kappagantula, Lance Zhang, Jerry P. Melchor, Johannes G. Reiter, Alexander Heyde, Craig M. Bielski, Alexander Penson, Mithat Gonen, Debyani Chakravarty, Eileen M. O'Reilly, Laura D. Wood, Ralph H. Hruban, Martin A. Nowak, Nicholas D. Socci, Barry S. Taylor, Christine A. Iacobuzio-Donahue
Article
Oncology
Caitlin A. McIntyre, Sharon A. Lawrence, Allison L. Richards, Joanne F. Chou, Winston Wong, Marinela Capanu, Michael F. Berger, Mark T. A. Donoghue, Kenneth H. Yu, Anna M. Varghese, David P. Kelsen, Wungki Park, Vinod P. Balachandran, T. Peter Kingham, Michael D'Angelica, Jeffrey A. Drebin, William R. Jarnagin, Christine A. Iacobuzio-Donahue, Peter J. Allen, Eileen M. O'Reilly
Article
Pathology
Marc Attiyeh, Lance Zhang, Christine Iacobuzio-Donahue, Peter Allen, Rami Imam, Olca Basturk, David S. Klimstra, Carlie S. Sigel
Article
Multidisciplinary Sciences
Heather J. Landau, Venkata Yellapantula, Benjamin T. Diamond, Even H. Rustad, Kylee H. Maclachlan, Gunes Gundem, Juan Medina-Martinez, Juan Arango Ossa, Max F. Levine, Yangyu Zhou, Rajya Kappagantula, Priscilla Baez, Marc Attiye, Alvin Makohon-Moore, Lance Zhang, Eileen M. Boyle, Cody Ashby, Patrick Blaney, Minal Patel, Yanming Zhang, Ahmet Dogan, David J. Chung, Sergio Giralt, Oscar B. Lahoud, Jonathan U. Peled, Michael Scordo, Gunjan Shah, Hani Hassoun, Neha S. Korde, Alexander M. Lesokhin, Sydney Lu, Sham Mailankody, Urvi Shah, Eric Smith, Malin L. Hultcrantz, Gary A. Ulaner, Frits van Rhee, Gareth J. Morgan, Ola Landgren, Elli Papaemmanuil, Christine Iacobuzio-Donahue, Francesco Maura
NATURE COMMUNICATIONS
(2020)
Editorial Material
Biochemistry & Molecular Biology
Joseph E. Grossman, Divya Vasudevan, Cailin E. Joyce, Manuel Hildago
Review
Gastroenterology & Hepatology
Akimasa Hayashi, Jungeui Hong, Christine A. Iacobuzio-Donahue
Summary: Pancreatic cancer is a genetic disease characterized by recurrent genetic alterations. Major roles have been identified for genetic alterations in complex systems such as SWI/SNF and COMPASS, as well as copy number alterations in genes like GATA6 and MYC. Developments in germline variants, mismatch repair deficiencies, and homologous recombination deficiencies highlight the shift towards precision medicine in pancreatic cancer research.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Review
Oncology
Bruno Bockorny, Joseph E. Grossman, Manuel Hidalgo
Summary: Pancreatic ductal adenocarcinoma (PDAC) remains a challenging cancer to treat. Chemotherapy has limited benefits and immunotherapy has made little progress. However, recent advances in understanding the tumor microenvironment and new approaches to immunotherapy have provided hope. Improvements in preclinical models, targeting the tumor microenvironment, and identifying biomarkers will likely lead to better selection of patients who could benefit from immunotherapy. Urgent research is needed to design effective combination trials to cure patients with PDAC.
CLINICAL CANCER RESEARCH
(2022)
Editorial Material
Gastroenterology & Hepatology
Christine A. Iacobuzio-Donahue
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Editorial Material
Oncology
Christine A. Iacobuzio-Donahue
Article
Oncology
Deepti Mathur, Chen Liao, Wendy Lin, Alessandro La Ferlita, Salvatore Alaimo, Samuel Taylor, Yi Zhong, Christine Iacobuzio-Donahue, Alfredo Ferro, Joao B. Xavier
Summary: Understanding the rewired metabolism underlying organ-specific metastasis in breast cancer is essential for improving the treatment and prevention of metastatic disease. A systems biology approach was used to compare metabolic fluxes in breast cancer cells and their derivatives with a tendency to metastasize to the brain or lung. The results showed that lung-homing cells had high glycolytic flux and a strong Warburg effect, associated with a high lactate dehydrogenase to pyruvate dehydrogenase ratio. This ratio was a significant predictor of lung metastasis, independent of other transcriptomic signatures, suggesting its potential as a biomarker.
Article
Biochemistry & Molecular Biology
Pashtoon Murtaza Kasi, Manuel Hidalgo, Mehraneh D. Jafari, Heather Yeo, Lea Lowenfeld, Uqba Khan, Alana T. H. Nguyen, Despina Siolas, Brandon Swed, Jini Hyun, Sahrish Khan, Madeleine Wood, Benjamin Samstein, Juan P. Rocca, Allyson J. Ocean, Elizabeta C. Popa, Daniel H. Hunt, Nikhil P. Uppal, Kelly A. Garrett, Alessio Pigazzi, Xi Kathy Zhou, Manish A. Shah, Erika Hissong
Summary: This study reports exceptional responses observed in patients with pMMR/MSS colon and rectal cancer treated with neoadjuvant botensilimab (BOT) and balstilimab (BAL). The findings have important implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy.
Article
Biotechnology & Applied Microbiology
Palash Sashittal, Haochen Zhang, Christine A. Iacobuzio-Donahue, Benjamin J. Raphael
Summary: This article introduces a new evolutionary model and algorithm, ConDoR, for inferring phylogeny in tumors. The model uses SNVs as phylogenetic markers and constrains losses of SNVs according to clusters of cells. The advantages of ConDoR are demonstrated through simulations and real data.
Article
Biochemistry & Molecular Biology
Pashtoon Murtaza Kasi, Manuel Hidalgo, Mehraneh D. Jafari, Heather Yeo, Lea Lowenfeld, Uqba Khan, Alana T. H. Nguyen, Despina Siolas, Brandon Swed, Jini Hyun, Sahrish Khan, Madeleine Wood, Benjamin Samstein, Juan P. Rocca, Allyson J. Ocean, Elizabeta C. Popa, Daniel H. Hunt, Nikhil P. Uppal, Kelly A. Garrett, Alessio Pigazzi, Xi Kathy Zhou, Manish A. Shah, Erika Hissong
Summary: Neoadjuvant botensilimab and balstilimab showed exceptional responses in patients with locally advanced mismatch repair proficient/microsatellite stable colon and rectal cancer. The observed rapid immune response pattern has not been previously described. Spatial biology analyses revealed the mechanism of action of botensilimab.
Article
Oncology
Manuel Hidalgo, Rocio Garcia-Carbonero, Kian-Huat Lim, Wells A. Messersmith, Ignacio Garrido-Laguna, Erkut Borazanci, Andrew M. Lowy, Laura Medina Rodriguez, Daniel Laheru, Beatriz Salvador-Barbero, Marcos Malumbres, David J. Shields, Joseph E. Grossman, Xin Huang, Meggan Tammaro, Jean-Francois Martini, Yanke Yu, Kenneth Kern, Teresa Macarulla
Summary: This study evaluates the clinical efficacy and safety of palbociclib plus nab-paclitaxel in patients with advanced pancreatic ductal adenocarcinoma. The preclinical and clinical data suggest that this combination treatment has antitumor activity and tolerable toxicity, but does not meet the prespecified efficacy threshold.
CANCER RESEARCH COMMUNICATIONS
(2022)