Article
Chemistry, Medicinal
Meredith S. Eno, Jason D. Brubaker, John E. Campbell, Chris De Savi, Timothy J. Guzi, Brett D. Williams, Douglas Wilson, Kevin Wilson, Natasja Brooijmans, Joseph Kim, Aysegul Ozen, Emanuele Perola, John Hsieh, Victoria Brown, Kristina Fetalvero, Andrew Garner, Zhuo Zhang, Faith Stevison, Rich Woessner, Jatinder Singh, Yoav Timsit, Caitlin Kinkema, Clare Medendorp, Christopher Lee, Faris Albayya, Alena Zalutskaya, Stefanie Schalm, Thomas A. Dineen
Summary: While EGFR tyrosine kinase inhibitors have revolutionized the treatment of NSCLC, the development of resistance mutations remains a challenge. This study introduces a novel reversible inhibitor, BLU-945, that shows promising activity against different resistance mutations. Clinical trials are currently underway to evaluate its efficacy and safety.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Milena Casula, Marina Pisano, Panagiotis Paliogiannis, Maria Colombino, Maria Cristina Sini, Angelo Zinellu, Davide Santeufemia, Antonella Manca, Stefania Casula, Silvia Tore, Renato Lobrano, Antonio Cossu, Giuseppe Palmieri
Summary: Oncogenic mutations in the EGFR gene are targets of tyrosine kinase inhibitors in lung adenocarcinoma patients. Liquid biopsy of ctDNA is increasingly used to detect EGFR mutations. This study compared three different techniques and found that real-time PCR-based methods showed equivalent detection ability to the NGS assay for circulating EGFR mutations, but the NGS assay had a poor ability to detect T790M.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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.
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
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
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
Huan-Ping Wang, Jun-Jun He, Qiao-Yun Zhu, Lin Wang, Jian-Hu Li, Jian-Song Huang, Wan-Zhuo Xie, Hong-Hu Zhu, Jie Jin
Summary: The NUP214-ABL1 fusion gene is commonly detected in T-ALL and B-ALL patients, but has not been reported in AML. The sensitivity of NUP214-ABL1-positive patients to TKIs remains controversial, and further case studies will provide insights into treatment and prognosis assessments.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Xiang-Meng Li, Wen-Feng Li, Jun-Tao Lin, Hong-Hong Yan, Hai-Yan Tu, Hua-Jun Chen, Bin-Chao Wang, Zhen Wang, Qing Zhou, Xu-Chao Zhang, Jian Su, Rui-Lian Chen, Yi-Long Wu, Jin-Ji Yang
Summary: Mutations in exon 4 and/or 7 of TP53 are promising predictive and prognostic indicators in EGFR-mutated NSCLC, potentially helping clinicians define precise target populations for treatment.
CLINICAL LUNG CANCER
(2021)
Article
Biochemistry & Molecular Biology
Hong-Yi Zhao, Xiao-Xiao Xi, Minhang Xin, San-Qi Zhang
Summary: The third-generation EGFR-TKIs have shown significant clinical achievements in NSCLC treatment, but acquired drug resistance remains a major limitation. The development of fourth-generation EGFR-TKIs targeting the triple mutant EGFR with C797S mutation has gained much attention. This review outlines the current panorama of fourth-generation EGFR-TKIs, focusing on their design strategy, binding mode, and antitumor activity. The challenges and prospects of fourth-generation EGFR-TKIs are also discussed.
BIOORGANIC CHEMISTRY
(2022)
Article
Oncology
Chien-Yu Lin, Chia-Hao Hu, Chia-Fu Hsu, Jeng-Shiuan Tsai, Chian-Wei Chen, Chia-Yin Lin, Chao-Chun Chang, Yi-Ting Yen, Yau-Lin Tseng, Po-Lan Su, Chien-Chung Lin
Summary: This retrospective study compared the treatment outcomes of patients with common and uncommon EGFR mutations in advanced-stage non-small cell lung cancer. The results showed that patients with uncommon EGFR mutations had poorer chemotherapy responses and shorter survival compared to those with common EGFR mutations. New treatment strategies are needed for these patients.
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
Oncology
Duanyang Peng, Pingan Liang, Congying Zhong, Peng Xu, Yanqing He, Yuxi Luo, Xia Wang, Anwen Liu, Zhimin Zeng
Summary: This study suggests that EGFR amplification is not an independent prognostic factor for progression-free survival (PFS) in advanced non-squamous NSCLC patients receiving first-line TKIs. However, it is an independent risk factor for PFS in the brain metastasis population.
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
Oncology
Yaping Zhang, Hui Wang, Xiaoyan Wang, Shuai Li, Hongming Fang
Summary: EGFR, ALK, and ROS1 mutations are typically considered mutually exclusive. This article describes a rare case of a patient with triple mutations in EGFR, ALK, and ROS1 in advanced NSCLC, who responded well to multiple treatment options with a slightly poorer overall survival than patients with single driver gene mutations.
CLINICAL LUNG CANCER
(2021)
Article
Oncology
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Summary: The study investigated the correlation between PIK3CA mutations and treatment response or duration in patients with HER2-positive breast cancer. The results showed that patients with activating PIK3CA mutations had lower pathologic complete response rates and shorter progression-free survival with HER2-targeted therapy. Precise targeted therapy is needed to improve survival of patients with HER2+/PIK3CA mutant breast cancer.
CANCER RESEARCH AND TREATMENT
(2023)
Article
Oncology
Yong Wha Moon, Seung Ki Kim, Keun Seok Lee, Moon Hee Lee, Yeon Hee Park, Kyong Hwa Park, Gun Min Kim, Seungtaek Lim, Seung Ah Lee, Jae Duk Choi, Eunhye Baek, Hyesun Han, Seungjae Baek, Seock-Ah Im
Summary: This study investigated the consistent efficacy and safety of eflapegrastim compared to pegfilgrastim in Koreans and Asians. The results showed that eflapegrastim was non-inferior to pegfilgrastim in terms of duration of severe neutropenia in Korean and Asian populations. The safety profiles of both drugs were similar across different patient populations.
CANCER RESEARCH AND TREATMENT
(2023)
Article
Oncology
Kyoungmin Lee, In Hae Park, Sang Cheul Oh, Jae Hong Seo, Min Ji Jeon, Eun Sang Yu, Dae Sik Kim, Chul Won Choi, Ah-reum Lim, Myung Han Hyun, Ju Won Kim, Jwa Hoon Kim, Yoon Ji Choi, Soohyeon Lee, Kyong Hwa Park, Yeul Hong Kim, Jung Yoon Choi, Jung Sun Kim, Se Ryeon Lee, Hwa Jung Sung, Eun Joo Kang
Summary: This study investigated the perception and safety profile of COVID-19 vaccines in cancer patients. The results showed that despite concerns about vaccine-related adverse events and negative effects on cancer treatment, the vaccines were well tolerated by cancer patients, with a safety profile consistent with that of the general population.
Article
Oncology
Min-Hee Ryu, Kyung Hee Lee, Lin Shen, Kun-Huei Yeh, Changhoon Yoo, Young Seon Hong, Young Iee Park, Sung Hyun Yang, Dong Bok Shin, Dae Young Zang, Won Ki Kang, Ik-Joo Chung, Yeul Hong Kim, Baek-Yeol Ryoo, Byung-Ho Nam, Young Soo Park, Yoon-Koo Kang
Summary: This study evaluated the efficacy and safety of sorafenib combined with capecitabine and cisplatin as first-line chemotherapy for advanced gastric cancer. The results showed that adding sorafenib did not provide additional benefits compared to chemotherapy alone in treating metastatic gastric cancer.
Article
Radiology, Nuclear Medicine & Medical Imaging
Sung Eun Song, Ok Hee Woo, Yongwon Cho, Kyu Ran Cho, Kyong Hwa Park, Ju Won Kim
Summary: This study investigated the use of machine learning approaches with breast magnetic resonance imaging (MRI)-derived multiparametric and radiomic features to predict axillary lymph node metastasis (ALNM) in stage I-II triple-negative breast cancer (TNBC) patients. The results showed that radiomic features had good diagnostic performance in predicting ALNM.
ACADEMIC RADIOLOGY
(2023)
Article
Oncology
Hoonji Oh, Ji Young You, Eun-Shin Lee, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Jung Seok An, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Summary: This study evaluated the incidence and risk factors for the development of treatment-related acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) in early breast cancer patients. The use of anthracycline-based adjuvant therapy significantly increased the risk of AML/MDS, with the risk persisting for at least 10 years.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Jianxin Shi, Kouya Shiraishi, Jiyeon Choi, Keitaro Matsuo, Tzu-Yu Chen, Juncheng Dai, Rayjean J. Hung, Kexin Chen, Xiao-Ou Shu, Young Tae Kim, Maria Teresa Landi, Dongxin Lin, Wei Zheng, Zhihua Yin, Baosen Zhou, Bao Song, Jiucun Wang, Wei Jie Seow, Lei Song, I-Shou Chang, Wei Hu, Li-Hsin Chien, Qiuyin Cai, Yun-Chul Hong, Hee Nam Kim, Yi-Long Wu, Maria Pik Wong, Brian Douglas Richardson, Karen M. Funderburk, Shilan Li, Tongwu Zhang, Charles Breeze, Zhaoming Wang, Batel Blechter, Bryan A. Bassig, Jin Hee Kim, Demetrius Albanes, Jason Y. Y. Wong, Min-Ho Shin, Lap Ping Chung, Yang Yang, She-Juan An, Hong Zheng, Yasushi Yatabe, Xu-Chao Zhang, Young-Chul Kim, Neil E. Caporaso, Jiang Chang, James Chung Man Ho, Michiaki Kubo, Yataro Daigo, Minsun Song, Yukihide Momozawa, Yoichiro Kamatani, Masashi Kobayashi, Kenichi Okubo, Takayuki Honda, Dean H. Hosgood, Hideo Kunitoh, Harsh Patel, Shun-ichi Watanabe, Yohei Miyagi, Haruhiko Nakayama, Shingo Matsumoto, Hidehito Horinouchi, Masahiro Tsuboi, Ryuji Hamamoto, Koichi Goto, Yuichiro Ohe, Atsushi Takahashi, Akiteru Goto, Yoshihiro Minamiya, Megumi Hara, Yuichiro Nishida, Kenji Takeuchi, Kenji Wakai, Koichi Matsuda, Yoshinori Murakami, Kimihiro Shimizu, Hiroyuki Suzuki, Motonobu Saito, Yoichi Ohtaki, Kazumi Tanaka, Tangchun Wu, Fusheng Wei, Hongji Dai, Mitchell J. Machiela, Jian Su, Yeul Hong Kim, In-Jae Oh, Victor Ho Fun Lee, Gee-Chen Chang, Ying-Huang Tsai, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Adeline Seow, Jae Yong Park, Sun-Seog Kweon, Kun-Chieh Chen, Yu-Tang Gao, Biyun Qian, Chen Wu, Daru Lu, Jianjun Liu, Ann G. Schwartz, Richard Houlston, Margaret R. Spitz, Ivan P. Gorlov, Xifeng Wu, Ping Yang, Stephen Lam, Adonina Tardon, Chu Chen, Stig E. Bojesen, Mattias Johansson, Angela Risch, Heike Bickeboeller, Bu-Tian Ji, H-Erich Wichmann, David C. Christiani, Gadi Rennert, Susanne Arnold, Paul Brennan, James McKay, John K. Field, Sanjay S. Shete, Loic Le Marchand, Geoffrey Liu, Angeline Andrew, Lambertus A. Kiemeney, Shan Zienolddiny-Narui, Kjell Grankvist, Mikael Johansson, Angela Cox, Fiona Taylor, Jian-Min Yuan, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Hyo-Sung Jeon, Shih Sheng Jiang, Jae Sook Sung, Chung-Hsing Chen, Chin-Fu Hsiao, Yoo Jin Jung, Huan Guo, Zhibin Hu, Laurie Burdett, Meredith Yeager, Amy Hutchinson, Belynda Hicks, Jia Liu, Bin Zhu, Sonja I. Berndt, Wei Wu, Junwen Wang, Yuqing Li, Jin Eun Choi, Kyong Hwa Park, Sook Whan Sung, Li Liu, Chang Hyun Kang, Wen-Chang Wang, Jun Xu, Peng Guan, Wen Tan, Chong-Jen Yu, Gong Yang, Alan Dart Loon Sihoe, Ying Chen, Yi Young Choi, Jun Suk Kim, Ho-Il Yoon, In Kyu Park, Ping Xu, Qincheng He, Chih-Liang Wang, Hsiao-Han Hung, Roel C. H. Vermeulen, Iona Cheng, Junjie Wu, Wei-Yen Lim, Fang-Yu Tsai, John K. C. Chan, Jihua Li, Hongyan Chen, Hsien-Chih Lin, Li Jin, Jie Liu, Norie Sawada, Taiki Yamaji, Kathleen Wyatt, Shengchao A. Li, Hongxia Ma, Meng Zhu, Zhehai Wang, Sensen Cheng, Xuelian Li, Yangwu Ren, Ann Chao, Motoki Iwasaki, Junjie Zhu, Gening Jiang, Ke Fei, Guoping Wu, Chih-Yi Chen, Chien-Jen Chen, Pan-Chyr Yang, Jinming Yu, Victoria L. Stevens, Joseph F. Fraumeni, Nilanjan Chatterjee, Olga Y. Gorlova, Chao Agnes Hsiung, Christopher I. Amos, Hongbing Shen, Stephen J. Chanock, Nathaniel Rothman, Takashi Kohno, Qing Lan
Summary: This study identified 12 novel susceptibility variants for lung adenocarcinoma and a total of 28 loci associated with the disease in East Asian populations. Additionally, new candidate genes were discovered, contributing to the understanding of the disease etiology. These findings have important implications for the research and translational applications of lung adenocarcinoma in individuals from East Asian populations.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
Summary: We investigated the genetic alterations in heavily treated HER2+ metastatic breast cancer patients. Through targeted sequencing of ctDNA, we identified 65 pathogenic gene alterations in 99 samples. TP53 and PIK3CA mutations, as well as higher ctDNA fraction, correlated with shorter progression-free survival. HRD-related gene mutations were more frequent in ctDNA and associated with resistance to treatment. New pathogenic variants were found at the end of treatment.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Ji Young You, Kyoung Hwa Park, Eun Sook Lee, Youngmee Kwon, Kyoung Tae Kim, Seungyoon Nam, Dong Hee Kim, Jeoung Won Bae
Summary: This study aimed to identify differentially expressed genes and pathways associated with good responses to anti-HER2 therapy and predict drug response in HER2-positive breast cancer patients undergoing neoadjuvant systemic therapy with trastuzumab. Analysis of RNA from tissue samples and cell lines revealed 6,656 differentially expressed genes, with 3,224 upregulated and 3,432 downregulated genes in trastuzumab-resistant cell lines. Changes in expression of 34 genes in various pathways were found to be related to the response to trastuzumab-containing treatment, affecting adhesion, extracellular matrix interactions, and phagosome action. This study provides insights into breast cancer signaling and potential predictions of therapeutic response to targeted therapies.
Article
Oncology
M. Kim, S. J. Shin, J. L. Lee, W. K. Bae, Y. J. Choi, J. Youk, C. Y. Ock, H. J. Lee, J. H. Byun, S. Kim, H. Song, K. H. Park, B. Keam
Summary: The efficacy and safety of trastuzumab-pkrb in combination with paclitaxel were evaluated in HER2-positive recurrent or metastatic urothelial carcinoma patients. The study showed promising efficacy and manageable toxicity profiles of this combination treatment in this type of cancer patients.
Article
Medicine, General & Internal
Sung Eun Song, Kyu Ran Cho, Yongwon Cho, Seung Pil Jung, Kyong-Hwa Park, Ok Hee Woo, Bo Kyoung Seo
Summary: This study assessed the false negative rate of axillary ultrasound (AUS) and the diagnostic performance of breast MRI and a nomogram in clinically T1-2 N0 breast cancer patients. The results showed that AUS had a false negative rate of approximately 20%, but the rate of high nodal burden was low. MRI had low positive predictive value but could reaffirm negative AUS with high negative predictive value.
JOURNAL OF KOREAN MEDICAL SCIENCE
(2023)
Article
Cell & Tissue Engineering
Eun Jung Lee, Kyoung Jin Lee, Seungpil Jung, Kyong Hwa Park, Serk In Park
Summary: Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells in the tumor microenvironment. The mechanism of MDSC mobilization from the bone marrow (BM) is still not fully understood. This study investigated the role of PTH1R activation in BM stromal cells in MDSC mobilization. It was found that PTH1R activation led to the release of monocytic (M-) MDSCs from murine BM by promoting binding between M-MDSCs and osteoblasts. The activation of Src family kinase and upregulation of proteases ADAM-17 and MMP7 were also involved in this process.
Article
Oncology
Se Hyun Kim, Seock-Ah Im, Koung Jin Suh, Kyung-Hun Lee, Min Hwan Kim, Joohyuk Sohn, Yeon Hee Park, Ji-Yeon Kim, Jae Ho Jeong, Kyoung Eun Lee, In Sil Choi, Kyong Hwa Park, Hee-Jun Kim, Eun Kyung Cho, So Yeon Park, Milim Kim, Jee Hyun Kim
Summary: This study evaluated the efficacy and safety of nivolumab and eribulin combination therapy for metastatic breast cancer in Asian populations. The results showed that this combination therapy had relatively good efficacy and tolerable safety in patients with hormone receptor-positive/HER2-negative and triple-negative breast cancer.
EUROPEAN JOURNAL OF CANCER
(2023)