Article
Oncology
Yalin Xie, Ning Su, Wei Zhou, An Lei, Xiang Li, Weiwei Li, Zhan Huang, Wenchang Cen, Jinxing Hu
Summary: For EGFR mutant LUAD patients, concurrent PTB can affect the efficacy of EGFR-TKI treatment, especially showing poorer survival outcomes.
CANCER MANAGEMENT AND RESEARCH
(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.
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)
Review
Oncology
Daisy Wai-Ka Chan, Horace Cheuk-Wai Choi, Victor Ho-Fun Lee
Summary: This study conducted a systematic review and meta-analysis to investigate the treatment-related adverse events (trAEs) of combined epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) and immune checkpoint inhibitor (ICI) in advanced non-small cell lung cancer (NSCLC). The results demonstrated a higher incidence of grade >= 3 trAEs in combination TKI and ICI, particularly in skin, gastrointestinal tract, and interstitial lung diseases. However, the interpretation of these results should be cautious due to the limited number of studies included in this meta-analysis.
Article
Oncology
Zhengyu Yang, Ya Chen, Yanan Wang, Shuyuan Wang, Minjuan Hu, Bo Zhang, Baohui Han
Summary: In advanced lung adenocarcinoma patients, patients with concurrent TP53 mutations have a shorter time to disease progression with EGFR-TKI monotherapy, but TKI combined with chemotherapy can reduce this heterogeneity.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Jiarong Tan, Chengping Hu, Pengbo Deng, Rongjun Wan, Liming Cao, Min Li, Huaping Yang, Qihua Gu, Jian An, Juan Jiang
Summary: Uncommon EGFR mutations in NSCLC show varying sensitivities to EGFR-TKIs, with Afatinib potentially being a better choice for most patients. Concurrent presence of 19del/L858R and tumor-suppressor gene alterations, especially TP53, can serve as prognostic biomarkers.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Dan Yan, Justus M. Huelse, Dmitri Kireev, Zikang Tan, Luxiao Chen, Subir Goyal, Xiaodong Wang, Stephen Frye, Madhusmita Behera, Frank Schneider, Suresh S. Ramalingam, Taofeek Owonikoko, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Summary: Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI). Activation of MERTK is associated with OSI resistance and inhibition of MERTK kinase can resensitize resistant cells to OSI.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Soon Hin How, Chong Kin Liam, Muhammad Adil Zainal Abidin, Harissa H. Hasbullah, Lye Mun Tho, Gwo Fuang Ho, Ibtisam Muhamad Nor, Yong Kek Pang, Kean Fatt Ho, Muthukkumaran Thiagarajan, Roziana Ariffin, Azlina Samsudin, Azza Omar, Sin Nee Tan, Choo Khoon Ong, Sing Yang Soon, Mau Ern Poh
Summary: This study describes the management and outcomes of EGFRm+ advanced NSCLC patients in an Asian cost-restrictive setting. The results suggest that the choice of first-line therapy, time on each line of treatment, and subsequent treatment options may adversely affect the overall survival of patients.
CANCER MANAGEMENT AND RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Byoung Chul Cho, Dong-Wan Kim, Alexander I. Spira, Jorge E. Gomez, Eric B. Haura, Sang-We Kim, Rachel E. Sanborn, Eun Kyung Cho, Ki Hyeong Lee, Anna Minchom, Jong-Seok Lee, Ji-Youn Han, Misako Nagasaka, Joshua K. Sabari, Sai-Hong Ignatius Ou, Patricia Lorenzini, Joshua M. Bauml, Joshua C. Curtin, Amy Roshak, Grace Gao, John Xie, Meena Thayu, Roland E. Knoblauch, Keunchil Park
Summary: This study evaluated the potential of combining amivantamab and lazertinib in patients with EGFR-mutated NSCLC. The results showed that this combination therapy had improved anti-tumor activity in some patients, with a safety profile similar to monotherapy.
Article
Oncology
Lingzhi Hong, Whitney E. Lewis, Monique Nilsson, Sonia Patel, Susan Varghese, Melvin J. Rivera, Robyn R. Du, Pingjun Chen, Haley N. Kemp, Waree Rinsurongkawong, Simon Heeke, Amy R. Spelman, Yasir Y. Elamin, Marcelo Negrao, Boris Sepesi, Don L. Gibbons, J. Jack Lee, Jia Wu, Natalie Vokes, John Heymach, Jianjun Zhang, Xiuning Le
Summary: The addition of anti-PD1 immunotherapy did not provide additional benefit to chemotherapy for EGFR-mutant LUAD patients with TKI resistance. However, there was a trend towards benefit with anti-VEGF therapy. The ideal choice for post-TKI treatment is still being evaluated.
Article
Multidisciplinary Sciences
Kuo-Hsuan Hsu, Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kang-Yi Su, Sung-Liang Yu, Jeremy J. W. Chen, Yen-Hsiang Huang, Gee-Chen Chang
Summary: Strong expressions of PD-L1 in treatment naive advanced EGFR-mutant NSCLC patients were associated with poor prognoses in those undergoing treatment with osimertinib as first-line therapy.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Jill Kolesar, Spencer Peh, Levin Thomas, Gayathri Baburaj, Nayonika Mukherjee, Raveena Kantamneni, Shirley Lewis, Ananth Pai, Karthik S. Udupa, Naveena Kumar An, Vivek M. Rangnekar, Mahadev Rao
Summary: Liquid biopsy and pharmacogenomic testing have potential applications in precision therapy for EGFR mutant and resistant lung cancers, allowing for precise treatment selection and monitoring of mutation development, as well as guiding dosing of EGFR TKIs.
Article
Oncology
Yen-Hsiang Huang, Kuo-Hsuan Hsu, Chun-Shih Chin, Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kang-Yi Su, Sung-Liang Yu, Jeremy J. W. Chen, Gee-Chen Chang
Summary: This study aimed to investigate the efficacy of different EGFR-TKIs plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients. The results showed that both erlotinib plus bevacizumab and afatinib plus bevacizumab as first-line treatment provided solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.
CANCER RESEARCH AND TREATMENT
(2022)
Article
Multidisciplinary Sciences
Sally J. Adua, Anna Arnal-Estape, Minghui Zhao, Bowen Qi, Zongzhi Z. Liu, Carolyn Kravitz, Heather Hulme, Nicole Strittmatter, Francesc Lopez-Giraldez, Sampada Chande, Alexandra E. Albert, Mary-Ann Melnick, Bomiao Hu, Katerina Politi, Veronica Chiang, Nicola Colclough, Richard J. A. Goodwin, Darren Cross, Paul Smith, Don X. Nguyen
Summary: The brain acts as a sanctuary site for metastatic cancer cells that can evade systemic therapies. In this study, the authors investigate the functional connection between drug resistance and central nervous system relapse in EGFR-mutant non-small cell lung cancer. They find that the brain microvascular tumor microenvironment is associated with the persistence of malignant cell sub-populations, which can proliferate in the brain as osimertinib-resistant lesions. This resistance is regulated by the RhoA/SRF signaling pathway. The authors also identify a genetic signature associated with osimertinib resistance in brain metastatic lesions.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Geunho Choi, Daegeun Kim, Junehwan Oh
Summary: This study utilized artificial intelligence to discover potential drugs that can overcome acquired resistance in lung cancer patients, reducing the limitations of the current drug discovery process.
FRONTIERS IN PHARMACOLOGY
(2021)
