Over-activation of the epidermal growth factor receptor (EGFR) is a hallmark of glioblastoma. However, EGFR-targeted therapies have led to minimal clinical response. While delivery of EGFR inhibitors (EGFRis) to the brain constitutes a major challenge, how additional drug-specific features alter efficacy remains poorly understood. We apply highly multiplex single-cell chemical genomics to define the molecular response of glioblastoma to EGFRis. Using a deep generative framework, we identify shared and drug-specific transcriptional programs that group EGFRis into distinct molecular classes. We identify programs that differ by the chemical properties of EGFRis, including induction of adaptive transcription and modulation of immunogenic gene expression. Finally, we demonstrate that pro-immunogenic expression changes associated with a subset of tyrphostin family EGFRis increase the ability of T-cells to target glioblastoma cells.
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http://dx.doi.org/10.1101/2024.04.08.587960 | DOI Listing |
Cureus
November 2024
Oncologic Dermatology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU.
J Am Acad Dermatol
November 2024
Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address:
Non-small cell lung cancer (NSCLC), the leading cause of cancer-related mortality worldwide, poses a formidable challenge due to its heterogeneity and the emergence of resistance to targeted therapies. While initially effective, first- and third-generation EGFR-tyrosine kinase inhibitors (TKIs) often fail to control disease progression, leaving patients with limited treatment options. To address this unmet medical need, we explored the therapeutic potential of multitargeting agents that simultaneously inhibit two key signalling pathways, the mesenchymal-epithelial transition factor (c-MET) and the G protein-coupled receptor Smoothened (SMO), frequently dysregulated in NSCLC.
View Article and Find Full Text PDFTransl Lung Cancer Res
October 2024
Division of Hematology and Oncology, Department of Internal Medicine, National Cancer Center Hospital, Goyang, Republic of Korea.
Background: Detailed clinical data about combination treatment with MET inhibitor (METi) and EGFR inhibitor (EGFRi) is lacking in patients with -mutant, -amplified, and EGFRi-resistant non-small cell lung cancer (NSCLC). This study aimed to report longitudinal data on the efficacy and safety of this combination treatment.
Methods: We retrospectively analyzed 44 patients with advanced -mutant and -amplified NSCLC who were treated with any types of METi plus EGFRi after progression with EGFRi at the National Cancer Center Hospital.
J Eur Acad Dermatol Venereol
October 2024
Oncodermatology Department, Cancer University Institute, Toulouse Oncopole, Toulouse, France.
Background: There is a need for unified guidance in the management of acneiform rash induced by epidermal growth factor receptor inhibitors (EGFRi) among dermatologists.
Objective: To establish unified international guidelines for the management of acneiform rash caused by EGFR inhibitors, based on an experts' Delphi consensus.
Methods: The initiative was led by five members of the European Academy of Dermatology and Venereology Task Force 'Dermatology for Cancer Patients' who developed a questionnaire that was circulated to a group of 32 supportive oncodermatology experts in Europe, Canada, Argentina, the US States and Asia.
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