Biogenesis, functions, and clinical implications of circular RNAs in non-small cell lung cancer

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide, with high morbidity and mortality. Non-small cell lung cancer (NSCLC) is a major pathological type of LC and accounts for more than 80% of all cases. Circular RNAs (circRNAs) are a large class of non-coding RNAs (ncRNAs) with covalently closed-loop structures, a high abundance, and tissue-specific expression patterns. They participate in various pathophysiological processes by regulating complex gene networks involved in proliferation, apoptosis, migration, and epithelial-to-mesenchymal transition (EMT), as well as metastasis. A growing number of studies have revealed that the dysregulation of circRNAs contributes to many aspects of cancer progression, such as its occurrence, metastasis, and recurrence, suggesting their great potential as efficient and specific biomarkers in the diagnosis, prognosis, and therapeutic targeting of NSCLC. In this review, we systematically elucidate the characteristics, biogenesis, and functions of circRNAs and focus on their molecular mechanisms in NSCLC progression. Moreover, we highlight their clinical implications in NSCLC treatment. READ ARTICLE

Molecular Therapy - Nucleic Acids DOI:10.1016/j.omtn.2021.11.013

Authors: Ying Liu, Xiang Ao, Wanpeng Yu, Yuan Zhang, Jianxun Wang

Short communication: The activity of brigatinib in patients with disease progression after next generation anaplastic lymphoma tyrosine kinase inhibitors...

Highlights:
- Brigatinib demonstrated activity in patients with disease progression after next-generation anaplastic lymphoma (ALK) tyrosine kinase inhibitors (TKI’s).
- The objective response was similar in patients who received next generation ALK inhibitors as first-line or second line therapy, and patients with and without brain metastases at baseline.
- Circulating tumor DNA testing (ctDNA) for ALK resistance mutations is feasible; however, a number of patients did not have detectable ctDNA or an ALK resistance mutations. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.12.019

Authors: Thomas E. Stinchcombe, Xiaofei Wang, Robert C. Doebele, Leylah M. Drusbosky, David E. Gerber, Leora Horn, Erin M. Bertino, Geoff Liu, Liza C. Villaruz, D. Ross Camidge

Clinical TrialsKirk SmithJanuary 3, 2022Targeted therapy, biomarker, ctDNA, liquid biopsy

How do you know if your cancer is ALK-positive?

Dr. Ross Camidge explains how a lung cancer patient knows if they have ALK-positive lung cancer. ALK is an important biomarker that can impact lung cancer treatment options. Talk to your doctor about comprehensive biomarker testing.

Visit Lung.org/alk for more information. Support for this educational program provided by Amgen, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Genentech, Lilly Oncology, Merck, Novartis and Pfizer.
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American Lung Association
Authors: Dr. Ross Camidge

VideoKirk SmithSeptember 14, 2020ALK, biomarker

Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial

Background: Ensartinib is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases. We aimed to assess the efficacy and safety of ensartinib in ALK-positive patients with non-small-cell lung cancer (NSCLC), in whom crizotinib therapy was unsuccessful. The associations between ensartinib efficacy and crizotinib-resistant mutations were also explored. Interpretation: Ensartinib has activity and is well tolerated in patients with crizotinib-refractory, ALK-positive NSCLC, including those with brain metastases. The role of ensartinib in patients in whom other second-generation ALK inhibitors have been unsuccessful warrants further studies. READ ARTICLE

The Lancet Respiratory Medicine DOI:10.1016/S2213-2600(19)30252-8

Authors: Yunpeng Yang, Jianya Zhou, Jianying Zhou, Jifeng Feng, Wu Zhuang, Prof Jianhua Chen, Jun Zhao, Wei Zhong, Yanqiu Zhao, Yiping Zhang, Yong Song, Yi Hu, Prof Zhuang Yu, Youling Gong, Yuan Chen, Feng Ye, Shucai Zhang, Lejie Cao, Yun Fan, Prof Gang Wu, Yubiao Guo, Chengzhi Zhou, Kewei Ma, Jian Fang, Weineng Feng, Prof Yunpeng Liu, Zhendong Zheng, Prof Gaofeng Li, Prof Ning Wu, Prof Wei Song, Xiaoqing Liu, Shijun Zhao, Lieming Ding, Prof Li Mao, Giovanni Selvaggi, Xiaobin Yuan, Yuanqing Fu, Tao Wang, Shanshan Xiao, Li Zhang

Advance of theragnosis biomarkers in lung cancer: from clinical to molecular pathology and biology

One distinct molecular subtype of non-small cell lung cancer (NSCLC) is defined by rearrangement of the anaplastic lymphoma kinase (ALK). The increasing knowledge over the last years has enabled the continuous improvement of ALK inhibitors; however, resistance in these patients remains a major concern. In this review, we summarize recent findings in ALK+-adenocarcinoma of the lung, highlighting the role of TP53 mutations in this specific cancer type and suggest new diagnostic strategies for the future, in order to improve patient’s outcome. READ ARTICLE

Journal of Thoracic Disease
DOI:10.21037/jtd.2018.12.03

Authors: Christina Alidousty, Till Baar, Carina Heydt, Svenja Wagener-Ryczek, Anna Kron, Juergen Wolf, Reinhard Buettner, Anne Maria Schultheis