Role of<i>STK11</i>in<i>ALK</i>‑positive non‑small cell lung cancer (Review)

Zhou, Wen; Yan, Lu-Da; Yu, Zhi-Qiong; Li, Na; Yang, Yaping; Wang, Meng; Chen, Yuanyuan; Mao, Meng-Xia; Peng, Xiaochun; Cai, Jun

doi:10.3892/ol.2022.13301

Cited by 4 publications

(3 citation statements)

References 133 publications

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“…As with tp53 mutations, co-occurring STK11 mutations in ALK -rearranged NSCLC predict an unfavorable response to targeted therapy. In NSCLC, patients with STK11 mutations had shorter overall survival (OS) and progression-free survival (PFS) than patients with STK11 wild-type who received immunotherapy or chemotherapy ( 15 ), it also tends to suggest that this patient may have a worse prognosis. Moreover, an extra PIK3CA E542K oncogenic mutation was detected in the patient’s plasma after her disease progressed despite treatment with ALK -TKIs.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Response to ALK-TKIs in a metastatic lung cancer patient with morphological heterogeneity and consistent molecular features

Liang

Liu

et al. 2023

Front. Oncol.

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Lung adenosquamous carcinoma (ASC) is a rare heterogeneous tumor containing two distinct components of adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). The limited biopsy sampling of the primary tumor might have overlooked either the ADC component or the SQCC component, resulting in a misdiagnosis of pure histology. Genotyping for driver mutations is now routinely performed in clinical settings to identify actionable oncogenic mutations and gene arrangements. Additionally, somatic mutations can potentially serve as a marker of clonal relationships. We report a rare case of ASC lung cancer, in which metastases were identified as ADC, while the primary was initially diagnosed as SQCC based on a fibrobronchoscope brush biopsy. The primary and metastatic tumors shared ALK rearrangement and other mutations support they were derived from a single clone origin. Our hypothesis is that the primary tumor contained a minor component of ADC that was not present in the histologic sections of lung biopsy. After sequential ALK-tyrosine kinase inhibitor (TKI) targeted therapy, both the patient’s primary lung tumor and the site of metastatic subcutaneous nodules decreased in size, with the metastatic sites demonstrating more noticeable shrinkage. However, after 11 months of targeted therapy, the patient was found to be resistant to ALK-TKIs. Subsequently, the patient’s respiratory status deteriorated rapidly, and a cycle of immunotherapy and chemotherapy did not show efficacy. To the best of our knowledge, this is a very rare case of lung ASC, disseminated metastasizing, with distinct morphology between the primary and metastases. Different therapeutic effects of ALK-TKIs were observed in two different morphological sites, with the metastatic cutaneous lesions shrinking more significantly than the primary lung lesions, though they both harbor the same EML4-ALK rearrangement. This case may provide diagnostic and therapeutic insights into lung ASC.

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Section: Discussionmentioning

confidence: 99%

Case Report: Response to ALK-TKIs in a metastatic lung cancer patient with morphological heterogeneity and consistent molecular features

Liang

Liu

et al. 2023

Front. Oncol.

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“…Nevertheless, exploring ALK's function, glycosylation impact, and cleavage mechanisms in NSCLC remains an uncharted territory. Therefore, future research should concentrate on elucidating the role of ALK in NSCLC, investigating how its glycosylation and cleav-age intricately contribute to treatment resistance, which is pivotal for advancing effective therapeutic interventions in NSCLC patients relying on ALK-targeted therapy [54].…”

Section: Alk Cleavage and Modificationsmentioning

confidence: 99%

“…on elucidating the role of ALK in NSCLC, investigating how its glycosylation and cleavage intricately contribute to treatment resistance, which is pivotal for advancing effective therapeutic interventions in NSCLC patients relying on ALK-targeted therapy [54].…”

Section: Alk Cleavage and Modificationsmentioning

confidence: 99%

Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions

Parvaresh,

Roozitalab,

Golandam

et al. 2024

Biomedicines

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Background and Objective: This review comprehensively explores the intricate landscape of anaplastic lymphoma kinase (ALK), focusing specifically on its pivotal role in non-small cell lung cancer (NSCLC). Tracing ALK’s discovery, from its fusion with nucleolar phosphoprotein (NPM)-1 in anaplastic large cell non-Hodgkin’s lymphoma (ALCL) in 1994, the review elucidates the subsequent impact of ALK gene alterations in various malignancies, including inflammatory myofibroblastoma and NSCLC. Approximately 3–5% of NSCLC patients exhibit complex ALK rearrangements, leading to the approval of six ALK-tyrosine kinase inhibitors (TKIs) by 2022, revolutionizing the treatment landscape for advanced metastatic ALK + NSCLC. Notably, second-generation TKIs such as alectinib, ceritinib, and brigatinib have emerged to address resistance issues initially associated with the pioneer ALK-TKI, crizotinib. Methods: To ensure comprehensiveness, we extensively reviewed clinical trials on ALK inhibitors for NSCLC by 2023. Additionally, we systematically searched PubMed, prioritizing studies where the terms “ALK” AND “non-small cell lung cancer” AND/OR “NSCLC” featured prominently in the titles. This approach aimed to encompass a spectrum of relevant research studies, ensuring our review incorporates the latest and most pertinent information on innovative and alternative therapeutics for ALK + NSCLC. Key Content and Findings: Beyond exploring the intricate details of ALK structure and signaling, the review explores the convergence of ALK-targeted therapy and immunotherapy, investigating the potential of immune checkpoint inhibitors in ALK-altered NSCLC tumors. Despite encouraging preclinical data, challenges observed in trials assessing combinations such as nivolumab-crizotinib, mainly due to severe hepatic toxicity, emphasize the necessity for cautious exploration of these novel approaches. Additionally, the review explores innovative directions such as ALK molecular diagnostics, ALK vaccines, and biosensors, shedding light on their promising potential within ALK-driven cancers. Conclusions: This comprehensive analysis covers molecular mechanisms, therapeutic strategies, and immune interactions associated with ALK-rearranged NSCLC. As a pivotal resource, the review guides future research and therapeutic interventions in ALK-targeted therapy for NSCLC.

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Unraveling the Potential of ALK-Targeted Therapies in NSCLC: Comprehensive Insights and Future Directions

Parvaresh,

Roozitalab,

Golandam

et al. 2024

Preprint

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The current review comprehensively explores the multifaceted landscape of anaplastic lymphoma kinase (ALK) and its pivotal role, specifically within non-small cell lung cancer (NSCLC). It traces the trajectory of ALK's discovery, notably its fusion with nucleolar phosphoprotein (NPM)-1 in anaplastic large cell non-Hodgkin's lymphoma (ALCL) in 1994. It unfolds the subsequent impact of ALK gene alterations across various malignancies, including inflammatory myofibroblastoma (IMT) and NSCLC. The prevalence of intricate ALK rearrangements affecting roughly 3–5% of NSCLC patients prompted the approval of six ALK-tyrosine kinase inhibitors (TKIs) by 2022, revolutionizing the treatment landscape for advanced metastatic ALK+ NSCLC. Second-generation TKIs like alectinib, ceritinib, and brigatinib have notably emerged to combat resistance issues initially associated with crizotinib, the pioneer ALK-TKI approval. Moreover, this review delves into the intersection of ALK and immunotherapy, exploring the potential of immune checkpoint inhibitors in ALK-altered NSCLC tumors. Despite promising preclinical data, challenges encountered in trials evaluating combinations like nivolumab-crizotinib, primarily due to severe hepatic toxicity, underscore the need for cautious exploration of these novel approaches. Additionally, the review delves into innovative avenues such as ALK vaccines and biosensors, shedding light on their promising potential within ALK-driven cancers. This comprehensive analysis encompasses molecular mechanisms, therapeutic strategies, and immune interactions associated with ALK-rearranged NSCLC. Ultimately, the review is a pivotal resource guiding future research and therapeutic interventions in ALK-targeted therapy for NSCLC.

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Role ofSTK11inALK‑positive non‑small cell lung cancer (Review)

Cited by 4 publications

References 133 publications

Case Report: Response to ALK-TKIs in a metastatic lung cancer patient with morphological heterogeneity and consistent molecular features

Case Report: Response to ALK-TKIs in a metastatic lung cancer patient with morphological heterogeneity and consistent molecular features

Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions

Unraveling the Potential of ALK-Targeted Therapies in NSCLC: Comprehensive Insights and Future Directions

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