Article
Oncology
Hiroshi Nokihara, Hirokazu Ogino, Atsushi Mitsuhashi, Kensuke Kondo, Ei Ogawa, Ryohiko Ozaki, Yohei Yabuki, Hiroto Yoneda, Kenji Otsuka, Yasuhiko Nishioka
Summary: These data suggest that the efficacy of osimertinib may differ between EGFR T790M-positive and -negative NSCLC patients with PE. The presence of PE was independently associated with shorter PFS and OS in EGFR T790M-positive NSCLC patients, but not in EGFR T790M-negative patients.
Article
Oncology
Yuki Katayama, Tadaaki Yamada, Keiko Tanimura, Shinsaku Tokuda, Kenji Morimoto, Soichi Hirai, Yohei Matsui, Ryota Nakamura, Masaki Ishida, Hayato Kawachi, Kazue Yoneda, Kazutaka Hosoya, Takahiro Tsuji, Hiroaki Ozasa, Akihiro Yoshimura, Masahiro Iwasaku, Young Hak Kim, Mano Horinaka, Toshiyuki Sakai, Takahiro Utsumi, Shinsuke Shiotsu, Takayuki Takeda, Ryohei Katayama, Koichi Takayama
Summary: In this study, it was found that epidermal growth factor receptor (EGFR) signaling is involved in adaptive resistance to lorlatinib in ALK-rearranged NSCLC. EGFR inhibition enhanced ALK inhibition-induced apoptosis and halted the proliferation of ALK-rearranged lung cancer cells. Combination therapy with EGFR inhibitor and lorlatinib significantly suppressed tumor regrowth after cessation of treatment. This study provides new insights into tumor evolution and the development of combined therapeutic strategies for ALK-rearranged lung cancer.
NPJ PRECISION ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Peijun Cao, Qingchun Zhao, Yongwen Li, Ruifeng Shi, Guangsheng Zhu, Zihe Zhang, Hongbing Zhang, Minghui Liu, Sen Wei, Hongyu Liu, Jun Chen
Summary: In this study, a patient with locally advanced lung adenocarcinoma received neoadjuvant chemotherapy and alectinib treatment, and then underwent thoracoscopic left lower lung lobectomy. After chemotherapy, the lymph nodes enlarged again and the patient was switched to alectinib therapy, but no significant lesion changes were detected on imaging. However, the pathological findings indicated extensive necrosis in the tumor area with no residual tumor cells and massive chronic inflammatory cell infiltration, which was inconsistent with the imaging results. The possibility of intratumoral immune heterogeneity was discussed as a potential explanation for this paradoxical response.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
Keiko Tanimura, Tadaaki Yamada, Koutaroh Okada, Kunihiro Nakai, Mano Horinaka, Yuki Katayama, Kenji Morimoto, Yuri Ogura, Takayuki Takeda, Shinsuke Shiotsu, Kosuke Ichikawa, Satoshi Watanabe, Yoshie Morimoto, Masahiro Iwasaku, Yoshiko Kaneko, Junji Uchino, Hirokazu Taniguchi, Kazue Yoneda, Satoaki Matoba, Toshiyuki Sakai, Hisanori Uehara, Seiji Yano, Tetsuro Kusaba, Ryohei Katayama, Koichi Takayama
Summary: This study elucidates the pivotal role of HER3 activation in the emergence of drug-tolerant cells in ALK-rearranged lung cancer, and finds that inhibiting HER3 signals combined with ALK-TKI treatment dramatically improves outcomes in ALK-rearranged lung cancer with mesenchymal features.
NPJ PRECISION ONCOLOGY
(2022)
Article
Oncology
Chi-Lu Chiang, Chia- Shen, Hsu-Ching Huang, Han-Jhih Chang, Yu-Ting Huang, Chao-Hua Chiu
Summary: This study investigates the optimal approach for EGFR mutation testing in NSCLC patients using centrifuged effusion samples and proposes a cytology-based specimen triage. The proposed strategy improves the detection rate of EGFR mutations and provides an efficient testing strategy for patients with EGFR-mutant NSCLC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Xiaoqian Zhai, Qiang Wu, Dan Pu, Liyuan Yin, Weiya Wang, Daxing Zhu, Feng Xu
Summary: A novel ALK fusion partner (ALK-GCA) and its sensitivity to alectinib in lung cancer were reported, highlighting the importance of detecting fusion mutations and reporting their response to guide treatment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Yi-Lin Chen, Wan-Li Chen, Yi-Chia Cheng, Ming-Ching Lin, Shu-Ching Yang, Hung-Wen Tsai, Chien-Chung Lin, Wu-Chou Su, Nan-Haw Chow, Chung-Liang Ho
Summary: A novel RNA-based ALK KD analysis was developed for screening ALK rearrangement in MPE and FFPE specimens of NSCLC. The test showed high sensitivity and specificity when compared with ALK IHC, making it a desirable screening tool with potential for routine diagnostics.
Review
Oncology
Savvas Papageorgiou, Sarah L. Pashley, Laura O'Regan, Sam Khan, Richard Bayliss, Andrew M. Fry
Summary: Lung cancer is a common and difficult-to-treat cancer. The EML4-ALK protein has been identified as a driving factor in a subset of lung cancer cases. While targeted inhibitors of ALK have shown initial effectiveness, resistance to these drugs develops over time. This review explores the resistance mechanisms and alternative treatment options for EML4-ALK-positive lung cancer patients, including approaches that target ALK-dependent signaling pathways and combination therapies.
Article
Oncology
Sarang S. Talwelkar, Mikko I. Mayranpaa, Julia Schuler, Nora Linnavirta, Annabrita Hemmes, Simone Adinolfi, Matti Kankainen, Wolfgang Sommergruber, Anna-Liisa Levonen, Jari Rasanen, Aija Knuuttila, Emmy W. Verschuren, Krister Wennerberg
Summary: Treatment with ALK inhibitors improves outcome for NSCLC patients with ALK-rearranged tumors, but resistance typically develops. In this study, tumor cell cultures were generated from an ALK-rearranged tumor specimen and drug screens identified a role for PI3K beta and EGFR inhibition in enhancing ALK-inhibitor response and preventing resistance. Combinatorial treatment with ALK and PI3K beta inhibitors showed promise in targeting ALK-rearranged NSCLC.
MOLECULAR ONCOLOGY
(2023)
Article
Cell Biology
Zhen Qin, Honghua Sun, Meiting Yue, Xinwen Pan, Liang Chen, Xinhua Feng, Xiumin Yan, Xueliang Zhu, Hongbin Ji
Summary: The EML4-ALK fusion is an important driver in the development of lung adenocarcinoma, with insights into its mechanism involving phase separation to form condensates that promote tumorigenesis. Targeting this process could present new therapeutic strategies for lung cancer patients with the EML4-ALK fusion.
Article
Pharmacology & Pharmacy
A. R. Bland, N. Shrestha, R. L. Bower, R. J. Rosengren, J. C. Ashton
Summary: Cell based studies have suggested that the combination of metformin with crizotinib may enhance the killing of ALK positive lung cancer cells and overcome crizotinib resistance. However, in vivo experiments using a xenograft mouse model showed that the combination did not result in greater tumor suppression compared to crizotinib alone. Additionally, metformin did not effectively overcome crizotinib resistance or directly induce cytotoxicity on cancer cells in this study.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Oncology
Kai Ou, Xiu Liu, Weihua Li, Yi Yang, Jianming Ying, Lin Yang
Summary: This study reported a 34-year-old patient with ALK rearrangement-positive and KRAS-wild pancreatic cancer, who showed significant responses to targeted therapies after developing resistance to chemotherapy, indicating that comprehensive molecular profiling for guiding targeted therapies can significantly improve survival outcomes for a subgroup of patients with pancreatic cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Yanping Su, Jiawen Yi, Yuan Zhang, Dong Leng, Xiaoxi Huang, Xinyu Shi, Yuhui Zhang
Summary: This study found that the EML4-ALK fusion protein enhances venous thromboembolism by regulating the expression of the coagulation factor TF. The pERK1/2-AP-1 pathway may be involved in this process.
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
(2023)
Article
Critical Care Medicine
Audra J. Schwalk, David E. Ost, Sahara N. Saltijeral, Henriette De La Garza, Roberto F. Casal, Carlos A. Jimenez, Georgie A. Eapen, Jeff Lewis, Waree Rinsurongkawong, Vadeerat Rinsurongkawong, Jack Lee, Yasir Elamin, Jianjun Zhang, Jack A. Roth, Stephen Swisher, John Heymach, Horiana B. Grosu
Summary: Patients with actionable mutations and those without mutations have similar risk of recurrent malignant pleural effusion, suggesting both groups may benefit from similar definitive management approaches. Larger pleural effusion size, higher pleural fluid lactate dehydrogenase levels, and positive cytologic examination results were associated with an increased hazard of recurrence.
Article
Critical Care Medicine
Benjamin J. Solomon, Todd M. Bauer, Tony S. K. Mok, Geoffrey Liu, Julien Mazieres, Filippo de Marinis, Yasushi Goto, Dong-Wan Kim, Yi-Long Wu, Jacek Jassem, Froylan Lopez Lopez, Ross A. Soo, Alice T. Shaw, Anna Polli, Rossella Messina, Laura Iadeluca, Francesca Toffalorio, Enriqueta Felip
Summary: After 3 years of follow-up, lorlatinib showed durable benefit over crizotinib in treatment-naive ALK-positive non-small-cell lung cancer patients, indicating the potential use of lorlatinib as a first-line treatment option.
LANCET RESPIRATORY MEDICINE
(2023)