Article
Biochemistry & Molecular Biology
Shiqi Ma, Lu Zhang, Yuan Ren, Wei Dai, Tingqing Chen, Liping Luo, Juan Zeng, Kun Mi, Jinyi Lang, Bangrong Cao
Summary: This study revealed the impact of EREG on EGFR-TKI sensitivity and its mechanisms in NSCLC, suggesting macrophage-produced EREG as a potential novel regulator and biomarker for EGFR-TKI therapy in NSCLC.
Review
Cell Biology
Dylan A. Farnsworth, Yankuan T. Chen, Georgia de Rappard Yuswack, William W. Lockwood
Summary: Mutant EGFR is a molecular driver of non-small cell lung cancer, and tumors with these mutations often rely on sustained oncogene signaling. While inhibiting EGFR with tyrosine kinase inhibitors has shown clinical benefits, resistance remains a challenge. The genetic mechanisms underlying EGFR dependency and factors allowing tumor cells to escape this dependency are still not fully understood.
Article
Chemistry, Multidisciplinary
Peijun Cao, Yongwen Li, Ruifeng Shi, Yin Yuan, Hao Gong, Guangsheng Zhu, Zihe Zhang, Chen Chen, Hongbing Zhang, Minghui Liu, Zhenhua Pan, Hongyu Liu, Jun Chen
Summary: Lung cancer has the highest mortality rate globally, and EGFR-TKIs have improved the survival of NSCLC patients by inducing autophagy. However, acquired resistance is common. Drug-resistant cells exhibit higher autophagy activity, and autophagy inhibitors can enhance the toxicity of EGFR-TKIs. Moreover, increased autophagy is associated with decreased EZH2 expression.
FRONTIERS IN CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Yi Li, Qing-Long Yu, Tong-Fang Li, Ya-Ni Xiao, Li Zhang, Qiu-Yan Zhang, Chun-Guang Ren, Hong-Lei Xie
Summary: The study demonstrates that the newly developed drug XHL11 exhibits strong anti-tumor activity against H1975 cells with EGFRL858R/T790M mutation and shows potential for therapeutic use in NSCLC patients. Additional research is needed to further explore the effectiveness and tolerability of XHL11 as an EGFR TKI.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Rashidi Dzul Keflee, Kok Hoong Leong, Satoshi Ogawa, Jerome Bignon, Mun Chiang Chan, Kin Weng Kong
Summary: This review provides an overview of the multifaceted mechanisms of resistance towards EGFR-TKIs, as well as the challenges and perspectives that should be addressed in strategising chemotherapeutic treatments to overcome the ever-evolving and adaptive nature of NSCLC.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Oncology
Yu-Ra Choi, Eun Hye Kang, Sunshin Kim, Seog-Yun Park, Ji-Youn Han, Youngjoo Lee
Summary: This study evaluated the efficacy of single MET inhibition in EGFR-mutant and MET-amplified lung cancer and found that it produced a short-lived response. Further research on novel combination therapy schedules is needed to achieve long-lasting efficacy with less toxicity.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Jun-Feng Liu, Xu-Sheng Sun, Jin-Huan Yin, Xi-E Xu
Summary: This retrospective study aimed to address the effect of adjuvant chemotherapy before adjuvant EGFR-TKI therapy and the duration of EGFR-TKI therapy on survival outcomes in patients with NSCLC. The results showed that adjuvant EGFR-TKI treatment was effective for patients with stage II-IIIA EGFR-mutation positive NSCLC. Patients with stage I and pathological risk factors were also suitable for receiving adjuvant EGFR-TKI therapy.
FRONTIERS IN ONCOLOGY
(2023)
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)
Review
Biochemistry & Molecular Biology
Julia Babuta, Zoe Hall, Toby Athersuch
Summary: This study critically reviewed the differences in metabolism between drug-resistant and drug-sensitive NSCLC cells, revealing distinct metabolic and lipidomic signatures in resistant cells. Differences in energy source reliance were observed between resistant and sensitive cell lines, suggesting that modulation of energy production pathways could potentially reverse drug resistance.
Review
Genetics & Heredity
Shigetoshi Nishihara, Toshimitsu Yamaoka, Fumihiro Ishikawa, Kensuke Higuchi, Yuki Hasebe, Ryo Manabe, Yasunari Kishino, Sojiro Kusumoto, Koichi Ando, Yusuke Kuroda, Tohru Ohmori, Hironori Sagara, Hitoshi Yoshida, Junji Tsurutani
Summary: Homeostasis is achieved by balancing cell survival and death. In cancer cells, this balance is disrupted, allowing for the survival and proliferation of dysregulated cells. The mechanisms by which EGFR-TKIs induce apoptosis, a form of cell death, are not fully understood. Understanding these mechanisms is crucial for developing strategies to overcome resistance or enhance the efficacy of EGFR-TKIs in treating EGFR-mutated NSCLC.
Article
Oncology
Lourdes Gutierrez, Ana Royuela, Enric Carcereny, Rafael Lopez-Castro, Delvys Rodriguez-Abreu, Bartomeu Massuti, Jose Luis Gonzalez-Larriba, Rosario Garcia-Campelo, Joaquim Bosch-Barrera, Maria Guirado, Carlos Camps, Manuel Domine, Reyes Bernabe, Joaquin Casal, Juana Oramas, Ana Laura Ortega, Ma Angeles Sala, Airam Padilla, David Aguiar, Oscar Juan-Vidal, Remei Blanco, Edel del Barco, Natividad Martinez-Banaclocha, Gretel Benitez, Blanca de Vega, Ainhoa Hernandez, Maria Saigi, Fernando Franco, Mariano Provencio
Summary: A prognostic model was developed using clinical and pathological variables to predict survival beyond 24 months in EGFR mutated NSCLC patients. Factors such as gender, mutation type, functional status, and metastatic sites were identified as predictors of long-term survival. The model showed good discrimination ability and could potentially assist clinicians in optimizing treatment strategies for this patient population.
Review
Oncology
Damien Reita, Lucile Pabst, Erwan Pencreach, Eric Guerin, Laurent Dano, Valerie Rimelen, Anne-Claire Voegeli, Laurent Vallat, Celine Mascaux, Michele Beau-Faller
Summary: Non-small cell lung cancer (NSCLC) is the most common cancer in the world. Activating EGFR gene mutations are predictive for the efficacy of EGFR tyrosine kinase inhibitors (TKIs). Acquired resistance is a challenge, leading to the search for novel biomarkers and drug targets that vary among different generations/lines of EGFR TKIs.
Review
Oncology
Xiaoshun Shi, Xiaoying Dong, Jianxue Zhai, Xiguang Liu, Di Lu, Zhen Ni, Hua Wu, Kaican Cai
Summary: Neoadjuvant EGFR-TKIs showed objective responses in approximately half of EGFR-sensitive NSCLC patients with a tolerable adverse effect profile. The impact of neoadjuvant EGFR-TKIs on survival remains inconclusive, and further evidence is needed to validate its favorable impact on NSCLC. The efficacy of neoadjuvant next-generation EGFR-TKIs in clinical trials remains unclear.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Min-Kyung Yeo, Yoonjoo Kim, Da Hye Lee, Chaeuk Chung, Go Eun Bae
Summary: This study found that the expression of NF-kappa B and AICDA increased in EGFR-TKI-resistant LAC, and the suppression of NF-kappa B and AICDA had a significant therapeutic effect in overcoming EGFR-TKI resistance.
Article
Chemistry, Multidisciplinary
Xing-mei Liang, Qiong Qin, Bo-ning Liu, Xiao-qing Li, Li-li Zeng, Jing Wang, Ling-ping Kong, Dian-sheng Zhong, Lin-lin Sun
Summary: The study reveals that DNA damage repair capacity is compromised in osimertinib-resistant cells, and inhibiting DNA-PK can increase sensitivity to osimertinib. Combination of osimertinib with DNA-PK inhibitors synergistically suppresses proliferation of resistant cells.
ACTA PHARMACOLOGICA SINICA
(2021)
Meeting Abstract
Oncology
J. Cohen, C. A. Natale, J. J. Lin, P. Lorusso, A. Mita, M. Mita, C. Y. Muller, M. Orloff, K. P. Papadopoulos, J. Rodon, T. K. Garyantes
ANNALS OF ONCOLOGY
(2022)
Article
Oncology
Jessica J. J. Lin, Justin F. F. Gainor
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Ibiayi Dagogo-Jack, Antonello Abbattista, John F. Murphy, Stan Krulewicz, Andrew Do, Jennifer Peterson, Jessica J. Lin, Justin F. Gainor, Rossella Messina, Elizabeth A. Krueger, Holger Thurm, Beow Y. Yeap
Summary: This study analyzed the safety profile of lorlatinib and identified several factors associated with developing neurocognitive adverse events (NAEs), including brain metastases, brain radiation, psychiatric illness, and the use of neurotropic medications.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Letter
Oncology
Or Kalchiem-Dekel, Christine M. Bestvina, Justin F. Gainor, Alexander Drilon, Jessica J. Lin
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Alexander Drilon, Joshua C. Horan, Anupong Tangpeerachaikul, Benjamin Besse, Sai-Hong Ignatius Ou, Shirish M. Gadgeel, D. Ross Camidge, Anthonie J. van der Wekken, Linh Nguyen-Phuong, Adam Acker, Clare Keddy, Katelyn S. Nicholson, Satoshi Yoda, Scot Mente, Yuting Sun, John R. Soglia, Nancy E. Kohl, James R. Porter, Matthew D. Shair, Viola Zhu, Monika A. Davare, Aaron N. Hata, Henry E. Pelish, Jessica J. Lin
Editorial Material
Critical Care Medicine
Jessica J. Lin, Justin F. Gainor
LANCET RESPIRATORY MEDICINE
(2023)
Article
Oncology
Joao V. Alessi, Arielle Elkrief, Biagio Ricciuti, Xinan Wang, Alessio Cortellini, Victor R. Vaz, Giuseppe Lamberti, Rosa L. Frias, Deepti Venkatraman, Claudia A. M. Fulgenzi, Federica Pecci, Gonzalo Recondo, Alessandro Di Federico, Adriana Barrichello, Hyesun Park, Mizuki Nishino, Grace M. Hambelton, Jacklynn V. Egger, Marc Ladanyi, Subba Digumarthy, Bruce E. Johnson, David C. Christiani, Xihong Lin, Justin F. Gainor, Jessica J. Lin, David J. Pinato, Adam J. Schoenfeld, Mark M. Awad
Summary: The efficacy of chemoimmunotherapy (CIT) in advanced NSCLC is associated with factors such as performance status, neutrophil-to-lymphocyte ratio, PD-L1 expression, and tumor mutational burden.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Review
Oncology
Jaime L. Schneider, Jessica J. Lin, Alice T. Shaw
Summary: Shaw and colleagues discuss the oncogenic roles of ALK in lung cancer, targeting approaches and the mechanisms underlying acquired resistance to ALK-directed therapy. Anaplastic lymphoma kinase (ALK) is a potent oncogenic driver in lung cancer. ALK tyrosine kinase inhibitors yield significant benefit in patients with ALK fusion-positive (ALK(+)) lung cancers; yet the durability of response is limited by drug resistance. Elucidation of on-target resistance mechanisms has facilitated the development of next-generation ALK inhibitors, but overcoming ALK-independent resistance mechanisms remains a challenge. In this Review, we discuss the molecular underpinnings of acquired resistance to ALK-directed therapy and highlight new treatment approaches aimed at inducing long-term remission in ALK(+) disease.
Meeting Abstract
Oncology
M. Hoejgaard, A. Drilon, J. J. Lin, S. Kummar, D. S. W. Tan, J. Patel, S. Leyvraz, V. Moreno Garcia, L. S. Rosen, B. Solomon, J. Yachnin, Y. Liu, M-S. Dai, R. Norenberg, D-I. Burcoveanu, L. Yun, G. Beckmann, C. E. Mussi, L. Shen
JOURNAL OF THORACIC ONCOLOGY
(2023)
Meeting Abstract
Oncology
M. L. Johnson, S-H. I. Ou, E. Felip, C. Baik, B. Besse, J. Mazieres, D. R. Camidge, S. Gadgeel, A. Drilon, Y. Y. Elamin, G. Liu, J. E. Reuss, T. Kehrig, H. E. Pelish, V. Zhu, J. J. Lin
JOURNAL OF THORACIC ONCOLOGY
(2023)
Meeting Abstract
Oncology
Marc Ladanyi, Sinchita Roy-Chowdhuri, Lauren Ritterhouse, Felix Sahm, Ricarda Norenberg, Kui Shen, Chi Chen, Marc Fellous, Nicoletta Brega, Cornelis M. van Tilburg, Jessica J. Lin, Marcia S. Brose, Ulrik N. Lassen, Ray McDermott, Theodore W. Laetsch, David S. Hong, Alexander Drilon, Erin R. Rudzinski
Meeting Abstract
Oncology
Hideko Isozaki, Ammal Abbasi, Naveed Nikpour, Marcello Stanzione, Ramin Sakhtemani, Susanna L. Monroe, Alice T. Shaw, Jessica J. Lin, Lecia V. Sequist, Zofia Piotrowska, Remi Buisson, Michael S. Lawrence, Aaron N. Hata
Meeting Abstract
Oncology
J. Alessi, A. Elkrief, B. Ricciuti, A. Cortellini, X. Wang, V. R. Vaz, A. Barrichello, G. Lamberti, C. Fulgenzi, F. Pecci, D. J. Pinato, A. J. Schoenfeld, M. M. Awad
JOURNAL OF THORACIC ONCOLOGY
(2022)
Article
Oncology
Aya Shiba-Ishii, Ted W. Johnson, Ibiayi Dagogo-Jack, Mari Mino-Kenudson, Theodore R. Johnson, Ping Wei, Scott L. Weinrich, Michele A. McTigue, Makeba A. Walcott, Linh Nguyen-Phuong, Kristin Dionne, Adam Acker, Lesli A. Kiedrowski, Andrew Do, Jennifer L. Peterson, Jaimie L. Barth, Beow Y. Yeap, Justin F. Gainor, Jessica J. Lin, Satoshi Yoda, Aaron N. Hata
Summary: This study identifies the spectrum of lorlatinib-resistant compound ALK mutations and identifies lorlatinib analogs that can overcome these compound mutations, providing different therapeutic strategies for precision targeting.
Article
Oncology
Ibiayi Dagogo-Jack, Geoffrey R. Oxnard, Makenzi Evangelist, Subba R. Digumarthy, Jessica J. Lin, Justin F. Gainor, John F. Murphy, Michael S. Rabin, Rebecca S. Heist, Alona Muzikansky, Alice T. Shaw
Summary: Lorlatinib demonstrated robust CNS activity in patients with CNS-only relapse on second-generation ALK inhibitors.
JCO PRECISION ONCOLOGY
(2022)