Review
Oncology
Mercedes Herrera-Juarez, Cristina Serrano-Gomez, Helena Bote-de-Cabo, Luis Paz-Ares
Summary: Precision oncology aims to design the best cancer treatment based on tumor biology. In NSCLC, patients with actionable genomic aberrations can benefit from targeted therapy, such as EGFR mutations and ALK rearrangements. Effective inhibitors have been developed for various druggable targets, leading to a paradigm shift in NSCLC treatment.
Article
Oncology
Roberto Chalela, Jose Gregorio Gonzalez-Garcia, Karys Khilzi, Victor Curull, Albert Sanchez-Font, Raquel Longaron, Maria Teresa Rodrigo-Calvo, Clara Martin-Ontiyuelo, Joaquim Gea, Beatriz Bellosillo
Summary: Driver mutations in non-tumoral lung cells were detected in a proportion of subjects with ADC, indicating their potential role in carcinogenesis. The presence of these mutations in the absence of coexisting mutations in the primary tumor was confirmed through highly sensitive PCR methods.
PATHOLOGY & ONCOLOGY RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Nguyen Quoc Khanh Le, Quang Hien Kha, Van Hiep Nguyen, Yung-Chieh Chen, Sho-Jen Cheng, Cheng-Yu Chen
Summary: The study introduced a machine learning model for selecting and predicting EGFR and KRAS mutations in NSCLC patients using a minimal number of semantic radiomics features, with the genetic algorithm plus XGBoost classifier showing the best accuracy in detecting these mutations. This noninvasive machine learning-based model demonstrated robust prediction of EGFR and KRAS mutations in patients with NSCLC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Haoyue Hu, Songtao Tan, Meng Xie, Peng Guo, Qiang Yu, Juan Xiao, Kangrui Zhao, Qiong Liao, Yi Wang
Summary: In non-small cell lung cancer, concurrent genetic alterations of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are rare, but their clinical and pathological characteristics are not well-defined, and the optimal treatment approach remains controversial. This report presents a case of stage IV lung adenocarcinoma with both EGFR and ALK mutations, along with high PD-L1 expression. The patient initially received treatment with EGFR tyrosine kinase inhibitors (TKIs), but the disease progressed, and regression was achieved following a switch to ALK-TKI therapy and local radiotherapy. Our report also provides a comprehensive summary of the clinical and pathological features, as well as treatment strategies, for NSCLC patients with concurrent EGFR mutation and ALK rearrangement.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Aaron C. Tan, Nick Pavlakis
Summary: The management of advanced lung cancer has been transformed by the identification of targetable oncogenic driver alterations, including ALK gene rearrangements. ALK tyrosine kinase inhibitors have become the first-line treatment options for advanced ALK rearranged NSCLC. However, drug resistance remains a challenge, and the role of anti-angiogenic therapy in ALK rearranged NSCLC needs further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Radiology, Nuclear Medicine & Medical Imaging
Giorgio Maria Agazzi, Marco Ravanelli, Elisa Roca, Daniela Medicina, Piera Balzarini, Carlotta Pessina, William Vermi, Alfredo Berruti, Roberto Maroldi, Davide Farina
Summary: The study aimed to develop a CT texture-based model to predict EGFR-mutated, ALK-rearranged lung adenocarcinomas and distinguish them from wild-type tumors. Results showed that texture analysis, particularly skewness values, could be promising for noninvasive characterization of lung adenocarcinoma with respect to EGFR and ALK mutations, achieving an average accuracy of 81.76% on the validation set.
Article
Oncology
I. Zerdes, C. Kamali, A. Koulouris, M. Elsayed, J. Schnorbach, P. Christopoulos, G. Tsakonas
Summary: The study validated the novel ALK-Brain Prognostic Index (ALK-BPI) for prognostic stratification of TKI-treated ALK+ NSCLC patients with brain metastases, providing an easy tool for clinical practice.
Article
Oncology
Yixiang Zhu, Ye Zhang, Xingsheng Hu, Mingzhao Wang, Hongyu Wang, Yutao Liu
Summary: ICI combined with chemotherapy +/- bevacizumab may be an effective and safe treatment option for EGFR/ALK-positive NSCLC patients, especially for those who progress after previous TKI therapy.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Biology
Isaac Shiri, Mehdi Amini, Mostafa Nazari, Ghasem Hajianfar, Atlas Haddadi Avval, Hamid Abdollahi, Mehrdad Oveisi, Hossein Arabi, Arman Rahmim, Habib Zaidi
Summary: This study investigated the impact of harmonization on the performance of radiomic features in predicting EGFR and KRAS mutation statuses in NSCLC patients. The results showed that harmonization improved the performance of features for EGFR prediction and significantly improved the performance of multivariate models for predicting both EGFR and KRAS mutations.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Editorial Material
Oncology
Shelley Kuang, Natasha B. Leighl
Summary: The study in NEJM examined whether lorlatinib should be the standard first-line treatment for advanced ALK-rearranged lung cancer.
Article
Oncology
Gang Xiao, Lifeng Li, Guilong Tanzhu, Zhiyuan Liu, Xuan Gao, Xin Wan, Desheng Xiao, Liu Chen, Xuefeng Xia, Rongrong Zhou
Summary: This study found that lung adenocarcinomas (LUAD) with EGFR-positive and ALK-positive had a suppressive tumor immune microenvironment (TIME) and were less responsive to immunotherapy. The TIME in patients with EGFR/ALK-positive LUAD brain metastases (BMs) was different from that in primary lung cancer. Evaluating the immune characteristics of LUAD BMs is important for clinical treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Ryohei Yoshida, Maria Saigi, Tetsuo Tani, Benjamin F. Springer, Hirofumi Shibata, Shunsuke Kitajima, Navin R. Mahadevan, Marco Campisi, William Kim, Yoshihisa Kobayashi, Tran C. Thai, Koji Haratani, Yurie Yamamoto, Shriram K. Sundararaman, Erik H. Knelson, Amir Vajdi, Israel Canadas, Ravindra Uppaluri, Cloud P. Paweletz, Juan J. Miret, Patrick H. Lizotte, Prafulla C. Gokhale, Pasi A. Janne, David A. Barbie
Summary: This study reveals that MET amplification upregulates CD73 to suppress tumor cell STING induction and T-cell responsiveness in TKI-resistant, EGFR-mutated lung cancer, identifying a strategy to enhance immunogenicity and improve treatment.
Article
Oncology
Yanhui Wan, Youhui Qian, Youyu Wang, Fuyuan Fang, Guodong Wu
Summary: This study investigated the prognostic value of Beclin 1, EGFR, and ALK in non-small cell lung cancer (NSCLC). It was found that high Beclin 1 expression and negative EGFR and ALK mutations were associated with better survival rate and longer progress-free survival.
Article
Hematology
Joanna Roopkumar, Shyam K. Poudel, Lorenzo Gervaso, Chandana A. Reddy, Vamsidhar Velcheti, Nathan A. Pennell, Keith R. McCrae, Alok A. Khorana
Summary: Patients with ALK-mutant advanced lung adenocarcinoma have the highest rate of TE, which is associated with worse survival across all molecular subtypes. These findings underscore the importance of considering thromboprophylaxis in clinical decision-making.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)