Article
Oncology
Ines Mota, Enrico Patrucco, Cristina Mastini, Navin R. Mahadevan, Tran C. Thai, Elisa Bergaggio, Taek-Chin Cheong, Giulia Leonardi, Elif Karaca-Atabay, Marco Campisi, Teresa Poggio, Matteo Menotti, Chiara Ambrogio, Dario L. Longo, Susan Klaeger, Hasmik Keshishian, Zsofia M. Sztupinszki, Zoltan Szallasi, Derin B. Keskin, Jonathan S. Duke-Cohan, Bruce Reinhold, Steven A. Carr, Catherine J. Wu, Kelly D. Moynihan, Darrell J. Irvine, David A. Barbie, Ellis L. Reinherz, Claudia Voena, Mark M. Awad, Rafael B. Blasco, Roberto Chiarle
Summary: Mota et al. demonstrate that immunogenic ALK peptides can enhance the response to immune checkpoint blockade in ALK-rearranged NSCLC mouse models. They also identify immunogenic human ALK peptides for future translational research.
Article
Oncology
Meichen Li, Xue Hou, Jing Chen, Baishen Zhang, Na Wang, Hongyu Han, Likun Chen
Summary: This study evaluated the impact of ALK fusion variants, concomitant mutations, and PD-L1 expression on the clinical response to second-generation ALK TKIs in patients with ALK-rearranged NSCLC. The results showed that ALK fusion variant 3a/b, concomitant mutations, and high PD-L1 expression were associated with unfavorable clinical response to second-generation TKIs.
Article
Cell Biology
Myung Chang Lee, Hongchen Cai, Christopher W. Murray, Chuan Li, Yan Ting Shue, Laura Andrejka, Andy L. He, Alessandra M. E. Hozlem, Alexandros P. Drainans, Julie H. Ko, Garry L. Coles, Christina Kong, Shirley Zhu, ChunFang Zhu, Jason Wang, Matt van de Rijn, Dmitri A. Petrov, Monte M. Winslow, Julien Sage
Summary: We developed a quantitative multiplexed approach based on lentiviral barcoding and CRISPR-Cas9-mediated genome editing to functionally study candidate regulators of tumor initiation and growth in small cell lung cancer (SCLC). Naphthalene pre-treatment enhanced lentiviral vector-mediated SCLC initiation and enabled high-throughput sequencing analysis of tumor clones. The analysis identified TSC1 in the PI3K-AKT-mTOR pathway as a robust tumor suppressor in SCLC. This approach will provide insight into drivers of SCLC and facilitate the development of precision therapies for specific SCLC genotypes.
Review
Oncology
Yu Lei, Yan Lei, Xiang Shi, Jingjing Wang
Summary: Non-small cell lung cancer (NSCLC) is a malignant tumor with a high morbidity and mortality rate, and the EML4-ALK fusion gene is one of the most important pathogenic driver genes of NSCLC. With the development of molecular targeted research, the introduction of four generations of targeted drugs for EML4-ALK has significantly benefited patients.
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.
Article
Oncology
Chang Liu, Cuicui Liu, Jiatao Liao, Jiani C. Yin, Xianghua Wu, Xinmin Zhao, Si Sun, Huijie Wang, Zhihuang Hu, Yao Zhang, Hui Yu, Yang Shao, Jialei Wang
Summary: In this study, the mutational landscape of ALK-positive advanced NSCLCs both at baseline and disease progression was profiled, and resistance mechanisms and molecular correlations of progression-free survival (PFS) in response to first-line crizotinib were characterized. Rational selection of subsequent ALK TKIs may be facilitated by these findings.
Article
Oncology
Zhifeng Ye, Junhua Guo
Summary: In this case report, a patient with lung adenocarcinoma was identified with EML4-ALK mutations after progressing on an immune checkpoint inhibitor. The patient was treated with alectinib and obtained a progression-free survival (PFS) of 24 months. Next-generation sequencing on circulating tumor DNA identified multiple ALK mutations, and the patient achieved a PFS of 5 months with ensartinib. Currently, the patient is still benefiting from lorlatinib treatment with a PFS over 10 months.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Ziyun Shen, Meixin Teng, Lu Han, Dongliang Bian, Jing Zhang, Xinsheng Zhu, Yang Qing, Shiqi Hu, Yan Chen, Wangchao Yao, Huansha Yu, Lele Zhang, Peng Zhang
Summary: This study suggests that NSCLC patients with KRAS driver mutations have a superior response to neoadjuvant immunotherapy, possibly due to their higher immunogenicity. The findings highlight the importance of considering oncogenic driver mutations in selecting neoadjuvant treatment strategies for NSCLC patients.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Oncology
Yuki Shimizu, Koutaroh Okada, Jun Adachi, Yuichi Abe, Ryohei Narumi, Ken Uchibori, Noriko Yanagitani, Sumie Koike, Satoshi Takagi, Makoto Nishio, Naoya Fujita, Ryohei Katayama
Summary: This study found that glycogen synthase kinase 3 (GSK3) plays a crucial role in both intermediate and acquired resistance to lorlatinib in ALK-positive NSCLC. Inhibiting GSK3 can suppress the growth of resistant cells and make other resistant cells sensitive to lorlatinib.
NPJ PRECISION ONCOLOGY
(2022)
Review
Oncology
Yan Xiang, Shiyu Zhang, Xiaoxu Fang, Yingying Jiang, Tingwen Fang, Jinwen Liu, Kaihua Lu
Summary: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases, and targeted therapy for specific fusion subtypes of the anaplastic lymphoma kinase (ALK) gene shows potential. However, the efficacy of ALK-TKIs in rare ALK fusions is still uncertain. This article summarizes the differential responses of several rare ALK fusions to ALK-TKIs and suggests treatment strategies for the rare ALK fusion population, aiming to guide the application of ALK-TKIs more effectively.
Article
Oncology
Jingjing Li, Bin Zhang, Yu Zhang, Feng Xu, Zhenfa Zhang, Lin Shao, Chunhe Yan, Paola Ulivi, Marc G. Denis, Petros Christopoulos, Vincent Thomas de Montpreville, Eric H. Bernicker, Anthonie J. van der Wekken, Changli Wang, Dongsheng Yue
Summary: This study retrospectively analyzed 96 NSCLC patients with ALK rearrangement, identifying TP53 mutations as the most common, along with other driver gene mutations. EML4-ALK fusions were the primary form identified, with novel non-EML4 translocation partners also discovered. Patients with PIK3R2 and PI3K signaling pathway alterations showed shorter survival outcomes.
TRANSLATIONAL LUNG CANCER RESEARCH
(2021)
Review
Oncology
Karan Seegobin, Umair Majeed, Nathaniel Wiest, Rami Manochakian, Yanyan Lou, Yujie Zhao
Summary: ICI therapy in NSCLC shows promising outcomes in certain cases with actionable mutations, but its efficacy remains unclear in other cases. The correlation between PD-L1 expression or tumor mutation burden and treatment outcome is inconclusive.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Hao Zeng, Yalun Li, Ye Wang, Meijuan Huang, Yan Zhang, Panwen Tian, Weimin Li
Summary: This study described a rare case of PDK1-ALK, STRN-ALK double-fusion variant in a patient with metastatic lung adenocarcinoma, who responded well to alectinib treatment. This suggests a promising therapeutic option for patients with rare ALK double-fusion variants.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Jia Zhong, Hua Bai, Zhijie Wang, Jianchun Duan, Wei Zhuang, Di Wang, Rui Wan, Jiachen Xu, Kailun Fei, Zixiao Ma, Xue Zhang, Jie Wang
Summary: With better understanding of driver mutations in NSCLC, the range of targeted therapy options has expanded, leading to improved survival and safety. However, responses to these therapies are often temporary and incomplete, and even patients with the same oncogenic driver gene can exhibit diverse responses. The role of immune-checkpoint inhibitors (ICIs) in NSCLC with driver mutations is still uncertain. This review aims to classify the management of NSCLC based on gene subtype, concomitant mutation, and dynamic alternation, and provides an overview of resistance mechanisms and potential therapeutic approaches.
FRONTIERS OF MEDICINE
(2023)
Article
Respiratory System
Yuan Yang, Baohua Lu, Mingming Hu, Qunhui Wang, Mei Jiang, Tongmei Zhang, Zhe Liu
Summary: This study analyzed the characteristics and prognostic values of ALK fusion gene partner, gene subtype, and abundance in advanced NSCLC patients with ALK positive, and explored the best treatment mode of ALK-TKIs. The results showed differences in abundance between different fusion partners and subtypes, and smoking was identified as a poor prognostic factor.
BMC PULMONARY MEDICINE
(2023)
Article
Respiratory System
Satu Maki-Nevala, Virinder Kaur Sarhadi, Aija Knuuttila, Ilari Scheinin, Pekka Ellonen, Sonja Lagstrom, Mikko Ronty, Eeva Kettunen, Kirsti Husgafvel-Pursiainen, Henrik Wolff, Sakari Knuutila
Article
Oncology
Satu Maki-Nevala, Virinder Kaur Sarhadi, Mikko Ronty, Eeva Kettunen, Kirsti Husgafvel-Pursiainen, Henrik Wolff, Aija Knuuttila, Sakari Knuutila
Article
Oncology
Noora Porkka, Satu Valo, Taina T. Nieminen, Alisa Olkinuora, Satu Maki-Nevala, Samuli Eldfors, Paivi Peltomaki
Meeting Abstract
Oncology
Noora Porkka, Alisa Olkinuora, Satu Maki-Nevala, Samuli Eldfors, Paivi Peltomaki
Article
Oncology
Katja Tuononen, Satu Maki-Nevala, Virinder Kaur Sarhadi, Aino Wirtanen, Mikko Ronty, Kaisa Salmenkivi, Jenny M. Andrews, Aino I. Telaranta-Keerie, Sari Hannula, Sonja Lagstrom, Pekka Ellonen, Aija Knuuttila, Sakari Knuutila
GENES CHROMOSOMES & CANCER
(2013)
Article
Oncology
Satu Maki-Nevala, Virinder Kaur Sarhadi, Katja Tuononen, Sonja Lagstrom, Pekka Ellonen, Mikko Ronty, Aino Wirtanen, Aija Knuuttila, Sakari Knuutila
GENES CHROMOSOMES & CANCER
(2013)
Article
Medicine, General & Internal
Satu Maki-Nevala, Satu Valo, Ari Ristimaki, Virinder Sarhadi, Sakari Knuutila, Minna Nystrom, Laura Renkonen-Sinisalo, Anna Lepisto, Jukka-Pekka Mecklin, Paivi Peltomaki
Article
Oncology
Satu Maki-Nevala, Sanjeevi Ukwattage, Alisa Olkinuora, Henrikki Almusa, Maarit Ahtiainen, Ari Ristimaki, Toni Seppala, Anna Lepisto, Jukka-Pekka Mecklin, Paivi Peltomaki
Summary: Ulcerative colitis increases the risk of colorectal cancer, and this study examined the genetic and epigenetic profiles of colitis-associated colorectal carcinomas (CA-CRC). Subgroups within CA-CRC were identified with different mutational loads and signatures, which may guide clinical management and therapy options. Lynch syndrome tumors showed a higher degree of hypermutability compared to CA-CRC subgroups.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Satu Maki-Nevala, Sanjeevi Ukwattage, Erkki-Ville Wirta, Maarit Ahtiainen, Ari Ristimaki, Toni T. Seppala, Anna Lepisto, Jukka-Pekka Mecklin, Paivi Peltomaki
Summary: Immunological and epigenetic changes play a role in tumorigenesis, with colitis-associated colorectal carcinomas (CA-CRC) and Lynch syndrome (LS) tumors showing differences in gene promoter methylation and immune cell distribution. CA-CRCs share a similar immune cell score and CD274 expression pattern with LS tumors, while increased methylation in normal mucosa may be a feature of CA-CRC-associated tumorigenesis.
Meeting Abstract
Biochemistry & Molecular Biology
S. Maki-Nevala, S. Valo, A. Ristimaki, V. K. Sarhadi, S. Knuutila, M. Nystrom, L. Renkonen-Sinisalo, A. Lepisto, J. Mecklin, P. Peltomaki
EUROPEAN JOURNAL OF HUMAN GENETICS
(2019)
Article
Oncology
Satu Maki-Nevala, Mikko Ronty, Mike Morel, Maria Gomez, Zoe Dawson, Virinder Kaur Sarhadi, Aino Telaranta-Keerie, Aija Knuuttila, Sakari Knuutila
JOURNAL OF THORACIC ONCOLOGY
(2014)