Transformation of invasive lung adenocarcinoma with ALK rearrangement into pulmonary sarcomatoid carcinoma

Xie, Xian-Jin; Chen, Xudong; Qi, Yiwen; Li, Mengmeng; Feng, Xiaoya

doi:10.1007/s00432-022-04022-0

Cited by 5 publications

(6 citation statements)

References 10 publications

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“… 17 , 18 A previous study indicated that mesenchymal-epithelial transition factor (MET) amplification or MET overexpression might be related to pathological sarcomatoid carcinoma transformation after TKI resistance in NSCLC patients with targetable genetic alterations but these findings were not present in our patient. 6 , 14 In particular, HLA class I antigen loss and a lack of β2-m expression are associated with decreased recognition of cancer cells by cognate CD8 + /granzyme B + T cells. HLA class I downregulation is widely recognized as a mechanism of tumor immune escape and has been associated with cancer immunotherapy resistance.…”

Section: Discussionmentioning

confidence: 99%

“… 3 Previous reports have shown that histological transformation is a well-described phenomenon and is one of the causes of tyrosine kinase inhibitor (TKI) resistance in NSCLC with EGFR- or ALK-rearranged adenocarcinoma. 4 – 6 The potential mechanism of acquired resistance to immunotherapy in NSCLC to small-cell lung cancer (SCLC) patients treated with ICIs has also been reported recently. 7 – 9 However, there have been no reports of histological transformation to pulmonary sarcomatoid carcinoma in NSCLC patients after immunotherapy.…”

Section: Introductionmentioning

confidence: 98%

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Histological sarcomatoid transformation in a lung adenocarcinoma patient following immune checkpoint blockade

Liang,

Guan,

Wang

et al. 2024

Ther Adv Med Oncol

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Histological transformation is a phenomenon that is well described as one of the causes of tyrosine kinase inhibitor resistance in oncogene-driven non-small-cell lung cancer (NSCLC). The use of immune checkpoint inhibitors (ICIs) as a potential mechanism of acquired resistance to immunotherapy in NSCLC to small-cell lung cancer was also recently found. Here, we report the histological transformation of sarcomatoid carcinoma and metastasis in a lung adenocarcinoma patient without targetable genetic alterations who experienced long-term disease remission after nivolumab therapy. The patient subsequently developed rapid progression in the mediastinal and retroperitoneal lymph nodes, bones, and small intestine. Surgical resection of the small intestine lesion due to acute small intestine bleeding revealed the transformation of NSCLC to sarcomatoid carcinoma. The patient died 3 months after sarcomatoid carcinoma transformation and extensive disease progression, although he was rechallenged with immunotherapy. Genomic and immunohistochemical analyses revealed a comparable abundance of gene mutations and a limited number of immune cells in the tumor microenvironment, with low infiltration of CD8+ T cells, CD4+ T cells, regulatory T cells, and PD-L1+ macrophages in metastatic tumors, revealing a noninflamed immune microenvironment for ICI-resistant tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Histological sarcomatoid transformation in a lung adenocarcinoma patient following immune checkpoint blockade

Liang,

Guan,

Wang

et al. 2024

Ther Adv Med Oncol

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“…EMT is another example of lineage plasticity that has been observed in ALK-positive lung adenocarcinoma following resistance to targeted therapies (2,10,(75)(76)(77).…”

Section: Epithelial-to-mesenchymal Transition (Emt)mentioning

confidence: 99%

Biology and impact of lineage plasticity in ALK-positive NSCLC: a narrative review

Meador¹,

Piotrowska²

2023

Transl Lung Cancer Res

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Background and Objective: Lineage transformation is a known mechanism of acquired resistance to targeted therapies in non-small cell lung cancer (NSCLC). Transformation to small cell and squamous carcinoma and epithelial-to-mesenchymal transition (EMT) have all been identified as recurrent but rare events in ALK-positive NSCLC. However, centralized data informing our understanding of the biology and clinical implications of lineage transformation in ALK-positive NSCLC are lacking.Methods: We performed a narrative review by searching the PubMed and clinicaltrials.gov databases for articles published in English from August, 2007 until October, 2022 and reviewing the bibliographies of key references to identify important literature related to lineage transformation in ALK-positive NSCLC.

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“…Akhoundova’s published work in the same journal that discusses the involvement of ALK in lung neuroendocrine tumors. 31–35…”

Section: Introductionmentioning

confidence: 99%

“…Akhoundova's published work in the same journal that discusses the involvement of ALK in lung neuroendocrine tumors. [31][32][33][34][35] According to Zhang's published work in the Journal of Thoracic Disease suggests that NAPSA serves as a valuable indicator for identifying lung adenocarcinoma. Li's published work in the same journal suggests that the presence of NAPSA expression is linked to a more favorable prognosis in individuals diagnosed with lung adenocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

A graphSAGE discovers synergistic combinations of Gefitinib, paclitaxel, and Icotinib for Lung adenocarcinoma management by targeting human genes and proteins: the RAIN protocol

Sadeghi,

Kiaei,

Boush

et al. 2024

Preprint

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Background: Adenocarcinoma of the lung is the most common type of lung cancer, and it is characterized by distinct cellular and molecular features. It occurs when abnormal lung cells multiply out of control and form a tumor in the outer region of the lungs. Adenocarcinoma of the lung is a serious and life-threatening condition that requires effective and timely management to improve the survival and quality of life of the patients. One of the challenges in this cancer treatment is finding the optimal combination of drugs that can target the genes or proteins that are involved in the disease process. Method: In this article, we propose a novel method to recommend combinations of trending drugs to target its associated proteins/genes, using a Graph Neural Network (GNN) under the RAIN protocol. The RAIN protocol is a three-step framework that consists of: 1) Applying graph neural networks to recommend drug combinations by passing messages between trending drugs for managing disease and genes that act as potential targets for disease; 2) Retrieving relevant articles with clinical trials that include those proposed drugs in previous step using Natural Language Processing (NLP); 3) Analyzing the network meta-analysis to measure the comparative efficacy of the drug combinations. Result: We applied our method to a dataset of nodes and edges that represent the network, where each node is a drug or a gene, and each edge is a p-value between them. We found that the graph neural network recommends combining Gefitinib, Paclitaxel, and Icotinib as the most effective drug combination to target this cancer associated proteins/genes. We reviewed the clinical trials and expert opinions on these medications and found that they support our claim. The network meta-analysis also confirmed the effectiveness of these drugs on associated genes. Conclusion: Our method is a novel and promising approach to recommend trending drugs combination to target cancer associated proteins/genes, using graph neural networks under the RAIN protocol. It can help clinicians and researchers to find the best treatment options for patients, and also provide insights into the underlying mechanisms of the disease.

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Transformation of invasive lung adenocarcinoma with ALK rearrangement into pulmonary sarcomatoid carcinoma

Cited by 5 publications

References 10 publications

Histological sarcomatoid transformation in a lung adenocarcinoma patient following immune checkpoint blockade

Histological sarcomatoid transformation in a lung adenocarcinoma patient following immune checkpoint blockade

Biology and impact of lineage plasticity in ALK-positive NSCLC: a narrative review

A graphSAGE discovers synergistic combinations of Gefitinib, paclitaxel, and Icotinib for Lung adenocarcinoma management by targeting human genes and proteins: the RAIN protocol

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