Case Report: A Case Report of a Histological Transformation of ALK-Rearranged Adenocarcinoma With High Expression of PD-L1 to Squamous Cell Carcinoma After Treatment With Alectinib

Zhang, Yan; Qin, Yijing; Xu, Hongen; Yao, Qihui; Gao, Yalan; Feng, Yuyao; Ren, Jingli

doi:10.3389/pore.2021.637745

Cited by 10 publications

(12 citation statements)

References 14 publications

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“…The development of a primary resistance mutation ALK :p.I1171N under crizotinib and alectinib therapy is well-described in the published literature ( Ou et al 2015 ). But the ensuing phenotypic switch from an ADC to a SqCC as evident by morphology and IHC is a rare event, which has been described previously in a couple of case reports only ( Table 1 ; Gong et al 2019 ; Park et al 2019 ; Kaiho et al 2020 ; Zhang et al 2021 ). Interestingly, the transdifferentiation occurred under targeted ALK–TKI-therapy in those five reported cases, in which the administration of alectinib at some point during treatment was a common aspect.…”

Section: Discussionsupporting

confidence: 86%

“…We support the transformation from ADC to SqCC as a possible alternative resistance mechanism under ALK–TKI-therapy similar to that shown in previous studies ( Gong et al 2019 ; Kaiho et al 2020 ; Park et al 2019 ; Zhang et al 2021 ). This case study highlights the benefit of comprehensive molecular testing and reveals the evolutionary connection of the lesions despite their histological differences.…”

Section: Discussionmentioning

confidence: 99%

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Histological and Molecular Plasticity of ALK-positive Non-Small-Cell Lung Cancer under Targeted Therapy - a Case Report

Ball

Christopoulos

Kirchner

et al. 2022

Cold Spring Harb Mol Case Stud

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With medical progress in cancer therapy, tyrosine kinase inhibitors (TKIs) became a standard of care for many cancer types. But the broad range of possible targeted therapies was accompanied by a plethora of potential resistance mechanisms, of which many have still to be identified. Here, we present the case of a patient with an EML4-ALK translocated non-small-cell lung cancer treated with four different TKIs. His tumor developed not only a well-known ALK-TKI resistance mutation, but also underwent a histological transformation from adenocarcinoma to squamous cell carcinoma. To confirm a shared monoclonal origin of the phenotypically different tumors, a phylogenetic reconstruction was conducted: this revealed a cluster of mutations including NFE2L2, KMT2D and MLH1 which are possible triggering events for the transformation.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Histological and Molecular Plasticity of ALK-positive Non-Small-Cell Lung Cancer under Targeted Therapy - a Case Report

Ball

Christopoulos

Kirchner

et al. 2022

Cold Spring Harb Mol Case Stud

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“…In NSCLC, histologic transformation from adenocarcinoma to small-cell or squamous cell lineage has been identified [62]. These changes have been described in lung adenocarcinoma with EGFR mutations, EML4-ALK fusions and KRAS G12 mutations treated with targeted therapies [63][64][65][66][67].…”

Section: 2bc Tumor Lineage Plasticitymentioning

confidence: 99%

Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer

2022

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Precision oncology has fundamentally changed how we diagnose and treat cancer. In recent years, there has been a significant change in the management of patients with oncogeneaddicted advanced-stage NSCLC. Increasing amounts of identifiable oncogene drivers have led to the development of molecularly targeted drugs. Undoubtedly, the future of thoracic oncology is shifting toward increased molecular testing and the use of targeted therapies. For the most part, these novel drugs have proven to be safe and effective. As with all great innovations, targeted therapies pose unique challenges. Drug toxicities, resistance, access, and costs are some of the expected obstacles that will need to be addressed. This review highlights some of the major challenges in the use of targeted therapies in NSCLC and provides guidance for the future strategies.

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“…HTs to SqCC have also been reported after the use of ALK-TKIs in several cases. 55 – 60 Two reports have demonstrated the paired pre- and post-treatment genomic landscape of the transformed ALK -rearranged SqCC; however, much remains unknown about HTs in SqCC. 57 , 58 …”

Section: Ht Induced By Agents Other Than Egfr-tkismentioning

confidence: 99%

“…HTs to SqCC have also been reported after the use of ALK-TKIs in several cases. [55][56][57][58][59][60] Two reports have demonstrated the paired pre-and post-treatment genomic landscape of the transformed ALK-rearranged SqCC; however, much remains unknown about HTs in SqCC. 57,58 Other molecular targeted agents for NSCLC HTs in patients with lung cancer are also caused by molecular targeted agents other than EGFR-and ALK-TKIs.…”

Section: Anaplastic Lymphoma Kinase-tkismentioning

confidence: 99%

Histologic transformation in lung cancer: when one door shuts, another opens

2022

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Histologic transformation (HT) is a major cause of drug resistance to therapy in patients with lung cancer. HTs to small-cell lung cancer (SCLC) have been reported frequently in patients with epidermal growth factor receptor ( EGFR)-mutated lung cancer. Although HTs have an impact on the clinical outcomes in patients owing to a high refractoriness to treatments, there is limited data on the prevalence, causes, mechanisms, treatment efficacy, and future treatment strategies. In this review, we assess the literature regarding HTs comprehensively, including those describing EGFR-tyrosine kinase inhibitors, other molecular targeted drugs, and immune checkpoint inhibitors. Furthermore, we discuss the mechanisms of HTs and the lineage plasticity to SCLC and squamous cell carcinoma in lung cancer. In addition, we summarize the treatment efficacy and future perspectives of HTs in patients with lung cancer, and propose better management strategies for this group of patients.

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Case Report: A Case Report of a Histological Transformation of ALK-Rearranged Adenocarcinoma With High Expression of PD-L1 to Squamous Cell Carcinoma After Treatment With Alectinib

Cited by 10 publications

References 14 publications

Histological and Molecular Plasticity of ALK-positive Non-Small-Cell Lung Cancer under Targeted Therapy - a Case Report

Histological and Molecular Plasticity of ALK-positive Non-Small-Cell Lung Cancer under Targeted Therapy - a Case Report

Challenges in the Use of Targeted Therapies in Non–Small Cell Lung Cancer

Histologic transformation in lung cancer: when one door shuts, another opens

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