Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview

Antoni, D.; Burckel, Hélène; Noël, Georges

doi:10.3390/cancers13102394

Cited by 6 publications

(3 citation statements)

References 100 publications

(117 reference statements)

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“…Timing of radiotherapy remains unclear, especially under different clinical settings. Furthermore, the safety of the combination of ALK TKIs and radiotherapy is unclear ( 115 ). Case reports using radiotherapy combined with alectinib and lorlatinib presented radiation-induced CNS necrosis, and this toxicity remains long after radiation ( 116 , 117 ).…”

Section: Alk Targeted Therapies In Nsclcmentioning

confidence: 99%

Targeting ALK Rearrangements in NSCLC: Current State of the Art

et al. 2022

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Anaplastic lymphoma kinase (ALK) alterations in non-small cell lung cancer (NSCLC) can be effectively treated with a variety of ALK-targeted drugs. After the approval of the first-generation ALK inhibitor crizotinib which achieved better results in prolonging the progression-free survival (PFS) compared with chemotherapy, a number of next-generation ALK inhibitors have been developed including ceritinib, alectinib, brigatinib, and ensartinib. Recently, a potent, third-generation ALK inhibitor, lorlatinib, has been approved by the Food and Drug Administration (FDA) for the first-line treatment of ALK-positive (ALK+) NSCLC. These drugs have manageable toxicity profiles. Responses to ALK inhibitors are however often not durable, and acquired resistance can occur as on-target or off-target alterations. Studies are underway to explore the mechanisms of resistance and optimal treatment options beyond progression. Efforts have also been undertaken to develop further generations of ALK inhibitors. This review will summarize the current situation of targeting the ALK signaling pathway.

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Section: Alk Targeted Therapies In Nsclcmentioning

confidence: 99%

Targeting ALK Rearrangements in NSCLC: Current State of the Art

et al. 2022

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“…Finally, the delivery of ICI and irradiation is an important issue as there appears to be variation in the focus of studies to date. Since some studies have analyzed their concurrent or non-concurrent use ( 145 ), while others have investigate drug use before, after, or currently with irradiation ( 26 , 211 ).…”

Section: Questions To Be Further Discussed and Consideredmentioning

confidence: 99%

International consensus on radiotherapy in metastatic non-small cell lung cancer

Zhu¹,

Ni²,

Cai³

et al. 2022

Transl Lung Cancer Res

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Background: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for most cases. While radiotherapy has historically served as a palliative modality in metastatic NSCLC, considerable advances in its technology and the continuous development of cutting-edge therapeutic agents, such as targeted therapy and immune checkpoint inhibitors (ICIs), are increasing its role in the multi-disciplinary management of the disease.Methods: International radiotherapy experts were convened to consider and reach consensuses on the clinical utilities of radiotherapy in metastatic NSCLC, with the aim to provide patient-focused, up to date, evidence-based, recommendations to assist cancer specialists in the management of patients with metastatic NSCLC worldwide.Results: Timely radiotherapy can offer rapid symptom alleviation and allow subsequent aggressive treatment approaches in patients with heavy tumor burden and/or oncologic emergencies. In addition, appropriate incorporation of radiotherapy as concurrent, consolidation, or salvage therapy makes it possible to achieve long-term survival, or even cure, for patients with oligo-metastatic disease. Cranial radiotherapy plays an important role in the management of brain metastasis, potentially augmenting the response and prolonging survival associated with targeted agents and ICIs. However, key questions remain, such as the appropriate choice of radiation techniques, optimal sequence of systemic therapies and radiotherapy, and optimal patient selection for such combination strategies. Although a strong rationale for combining radiotherapy and ICIs exists, its optimal parameters in this setting remain to be established. Conclusions:In the modern era, radiotherapy serves not only as a palliative tool in metastatic NSCLC, but also plays active roles in patients with oligo-focal disease, CNS metastasis and receiving ICIs.

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“…NSCLC treatment has been greatly promoted in recent years, benefiting from measures such as early screening programs, treatment strategy improvement, individualized and precise medicine, and novel targeted drug development (4)(5)(6)(7). In particular, along with the progression of molecular biotechnology, emerging treatment targets have been identified, and corresponding inhibitors have been developed, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), anaplastic lymphoma kinase (ALK) TKIs, and antiangiogenic drugs (8)(9)(10). However, even though the above improvements have been realized, the prognosis of NSCLC is still dismal; therefore, efforts continue to explore the underlying pathogenesis of NSCLC to develop more treatment targets to further prolong the survival of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

Microarray Identifies a Key Carcinogenic Circular RNA 0008594 That Is Related to Non-Small-Cell Lung Cancer Development and Lymph Node Metastasis and Promotes NSCLC Progression by Regulating the miR-760-Mediated PI3K/AKT and MEK/ERK Pathways

et al. 2021

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PurposeThis study aimed to explore the circular RNA (circRNA/circ) profile engaged in non-small cell lung cancer (NSCLC) development and metastasis and to investigate potentially key carcinogenic circRNAs related to NSCLC.MethodsCircRNA profiles between 10 NSCLC tissues and 10 adjacent tissues and between five NSCLC tissues with lymph node metastasis (LNM) and five NSCLC tissues without LNM were detected by Arraystar Human circRNA Array followed by bioinformatics. Circ_0008594 knockdown, circ_0004293 overexpression, and circ_0003832 overexpression plasmids were transfected into H23 and H460 cells to sort potential oncogenic circRNA. Then circ_0008594 overexpression and knockdown plasmids were transfected, followed by that circ_0008594 knockdown plus miR-760 knockdown plasmids were transfected into these cells. Cell proliferation, apoptosis, invasion, stemness, and pathways were detected. In addition, xenograft mice models were constructed via injecting H23 cells with circ_0008594 overexpression or knockdown to validate the findings.ResultsA total of 455 dysregulated circRNAs in NSCLC tissues versus adjacent tissues and 353 dysregulated circRNAs in NSCLC tissues with LNM versus those without LNM were discovered. Via cross-analysis, 19 accordant circRNAs were uncovered, among which three candidate circRNAs (circ_0008594, circ_0004293, circ_0003832) were chosen for functional experiments, during which it was observed that circ_0008549 affected H23 and H460 cell proliferation and apoptosis more obviously than circ_0004293 and circ_0003832. Subsequent experiments showed that circ_0008594 promoted H23 and H460 cell proliferation and invasion but affected stemness less and negatively regulated miR-760 via direct binding. Furthermore, miR-760 attenuated the effect of circ_0008549 on regulating H23 and H460 cell functions and the PI3K/AKT and MEK/ERK pathways. In vivo experiments further confirmed that circ_0008549 increased tumor volume, epithelial-mesenchymal transition, and the PI3K/AKT and MEK/ERK pathways while reducing tumor apoptosis and miR-760 NSCLC xenograft models.ConclusionOur study identifies several valuable circRNAs related to NSCLC development and LNM. Furthermore, as a key functional circRNA, circ_0008594 was observed to promote NSCLC progression by regulating the miR-760-mediated PI3K/AKT and MEK/ERK pathways.

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Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview

Cited by 6 publications

References 100 publications

Targeting ALK Rearrangements in NSCLC: Current State of the Art

Targeting ALK Rearrangements in NSCLC: Current State of the Art

International consensus on radiotherapy in metastatic non-small cell lung cancer

Microarray Identifies a Key Carcinogenic Circular RNA 0008594 That Is Related to Non-Small-Cell Lung Cancer Development and Lymph Node Metastasis and Promotes NSCLC Progression by Regulating the miR-760-Mediated PI3K/AKT and MEK/ERK Pathways

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