Article
Biology
Carolina Franco Nitta, Ellen W. Green, Elton D. Jhamba, Justine M. Keth, Irais Ortiz-Caraveo, Rachel M. Grattan, David J. Schodt, Aubrey C. Gibson, Ashwani Rajput, Keith A. Lidke, Bridget S. Wilson, Mara P. Steinkamp, Diane S. Lidke
Summary: Crosstalk between EGFR and RON is unidirectional, with EGFR phosphorylating RON to activate RON-directed signaling, which requires the formation of a signaling competent EGFR dimer. Nanoscale imaging reveals association of EGFR and RON in common plasma membrane microdomains, while two-color single particle tracking captures the formation of complexes between RON and EGF-bound EGFR.
Article
Cell Biology
Pinar Ozden Eser, Raymond M. Paranal, Jieun Son, Elena Ivanova, Yanan Kuang, Heidi M. Haikala, Ciric To, Jeffrey J. Okoro, Kshiti H. Dholakia, Jihyun Choi, Yoonji Eum, Atsuko Ogino, Pavlos Missios, Dalia Ercan, Man Xu, Michael J. Poitras, Stephen Wang, Kenneth Ngo, Michael Dills, Masahiko Yanagita, Timothy Lopez, Mika Lin, Jeanelle Tsai, Nicolas Floch, Emily S. Chambers, Jennifer Heng, Rana Anjum, Alison D. Santucci, Kesi Michael, Alwin G. Schuller, Darren Cross, Paul D. Smith, Geoffrey R. Oxnard, David A. Barbie, Lynette M. Sholl, Magda Bahcall, Sangeetha Palakurthi, Prafulla C. Gokhale, Cloud P. Paweletz, George Q. Daley, Pasi A. Janne
Summary: Some EGFR-mutant, MET-amplified lung cancers may develop dependence on MET activation alone, suggesting that these patients could be treated with a single-agent MET TKI instead of the current standard-of-care EGFR and MET inhibitor combination regimens.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Minling Gao, Yi Fu, Weiqiang Zhou, Gege Gui, Bachuchu Lal, Yunqing Li, Shuli Xia, Hongkai Ji, Charles G. Eberhart, John Laterra, Mingyao Ying
Summary: This study focuses on uncovering the key signaling pathways of EGFR/TAF, and identifies osimertinib as an effective inhibitor that can treat cancers like GBM effectively.
Review
Biochemistry & Molecular Biology
Manali Tilak, Jennifer Holborn, Laura A. New, Jasmin Lalonde, Nina Jones
Summary: Glioblastoma multiforme (GBM) is a deadly cancer with limited response to existing therapies. Subtypes of GBM with distinct genetic signatures show aberrant activation of signal transduction pathways. Current research focuses on understanding these molecular alterations to develop more efficient targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Jennifer Soler Beatty, Cristina Molnar, Carlos M. Luque, Jose F. de Celis, Maria D. Martin-Bermudo
Summary: The study identified a novel EGFR inhibitor named EGFRAP, which enhances the overgrowth induced by activated Ras and is upregulated in regions with active EGFR/Ras pathway. EGFRAP acts as a negative regulator of the EGFR/Ras pathway and its expression is regulated by the Notch pathway under normal and oncogenic conditions.
Review
Pharmacology & Pharmacy
Yazan Haddad, Marek Remes, Vojtech Adam, Zbynek Heger
Summary: The study utilized variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. These families shared similar mutational profiles, ligand R-groups facing the C-helix, mutation sites, and DFG domain.
DRUG DISCOVERY TODAY
(2021)
Article
Medicine, Research & Experimental
Hui Hua, Jiajia Zeng, Haixin Xing, Yuxin He, Linyu Han, Nasha Zhang, Ming Yang
Summary: This study systematically evaluated the role of genetic variants in A-to-I editing genes on the prognosis of NSCLC patients receiving EGFR-TKIs therapy. The researchers identified several SNPs in the ADAR gene that were significantly associated with patient prognosis and found that silencing ADAR enhanced the sensitivity of NSCLC cells to gefitinib. These findings highlight the importance of A-to-I RNA editing in drug resistance and suggest ADAR as a potential therapeutic target for unresectable NSCLC.
Article
Oncology
Youcef Ounoughene, Elise Fourgous, Yvan Boublik, Estelle Saland, Nathan Guiraud, Christian Recher, Serge Urbach, Philippe Fort, Jean-Emmanuel Sarry, Didier Fesquet, Serge Roche
Summary: The human kinome includes about 50 pseudo-kinases with unclear function, but they play important roles in cancer similar to active kinases. PEAK1, PEAK2, and PEAK3 pseudo-kinases are key components in the protein tyrosine kinase pathway, signaling via a SHED module, potentially promoting tumorigenesis.
Review
Oncology
Hideki Yamaguchi, Yuko Nagamura, Makoto Miyazaki
Summary: Gastric cancer is a leading cause of cancer-related death globally, with diffuse-type gastric carcinoma exhibiting aggressive progression and high recurrence rate. Gene amplification and aberrant activation of receptor tyrosine kinase signaling play a crucial role in the development and peritoneal metastasis of diffuse-type gastric carcinoma.
Review
Chemistry, Medicinal
Saloni Ramani, Sayalee Samant, Sonal M. Manohar
Summary: EGFR plays a significant role in cellular processes such as growth, survival, and differentiation. Its deregulation is implicated in various human malignancies, making it an attractive anticancer target. Current therapeutic strategies show some efficacy in inhibiting EGFR, but resistance limits their clinical benefit.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Hiromi Watanabe, Eiki Ichihara, Hiroe Kayatani, Go Makimoto, Kiichiro Ninomiya, Kazuya Nishii, Hisao Higo, Chihiro Ando, Sachi Okawa, Takamasa Nakasuka, Hirohisa Kano, Naofumi Hara, Atsuko Hirabae, Yuka Kato, Takashi Ninomiya, Toshio Kubo, Kammei Rai, Kadoaki Ohashi, Katsuyuki Hotta, Masahiro Tabata, Yoshinobu Maeda, Katsuyuki Kiura
Summary: Combination therapy with VEGFR2 blockade and molecular targeted agents showed significant anti-tumor effects in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. The study suggests that targeting VEGFR2 signaling may be a promising treatment strategy for oncogene-driven NSCLC.
Article
Biochemistry & Molecular Biology
Erik Wahlen, Frida Olsson, Doroteya Raykova, Ola Soderberg, Johan Heldin, Johan Lennartsson
Summary: This study investigates the internalization process of EGFR and PDGFR-β using immunofluorescent microscopy. The results show that these two receptors utilize separate internalization routes, but merge in a common endosomal compartment after 45 minutes of stimulation. The association between EGFR and caveolin-1 is stronger compared to PDGFR-β, and disruption of lipid rafts affects the signaling of EGFR and PDGFR-β differently.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Celine Greco, Anne-Charlotte Ponsen, Stephanie Leclerc-Mercier, Joel Schlatter, Salvatore Cisternino, Claude Boucheix, Christine Bodemer
Summary: This study investigated the possibility of using erlotinib and lapatinib to treat painful palmoplantar keratoderma in patients with pachyonychia congenita. The results showed that oral erlotinib at a dose of 75 mg/day could alleviate pain and reduce hyperkeratosis to some extent. Oral lapatinib, while reducing pain and improving symptoms, also had side effects. The effectiveness of erlotinib cream was inconclusive. Oral Her1 or 1/2 inhibitors offer promising therapeutic perspectives for patients with pachyonychia congenita.
Review
Chemistry, Medicinal
Adileh Ayati, Setareh Moghimi, Mahsa Toolabi, Alireza Foroumadi
Summary: Despite advancements in cancer treatment, EGFR inhibitors have shown significant improvement in targeted therapy. However, the emergence of epigenetic mutation and resistance issues have limited their effectiveness, leading to the need for further research in this field. Recent studies have focused on genetic alterations in the EGFR tyrosine kinase domain, resulting in the development of more selective and effective inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Jingyun Chen, Jiajun Liu, Baixue Xu, Yiou Cao, Xin Liang, Fanhong Wu, Xiaodong Shen, Xiaoying Ma, Jianwen Liu
Summary: This study demonstrates that the combination therapy of EBTP with TKIs can effectively inhibit the proliferation and angiogenesis of liver cancer cells, and reduce toxic effects. EBTP/Afa targets liver cancer cells and tumor vasculature, inhibiting their proliferation, motion, and angiogenesis.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)