ROS1-positive non-small cell lung cancer (NSCLC): biology, diagnostics, therapeutics and resistance

Yu, Zhi-Qiong; Wang, Meng; Zhou, Wen; Mao, Meng-Xia; Chen, Yuanyuan; Li, Na; Peng, Xiaochun; Cai, Jun; Cai, Zhiqiang

doi:10.1080/1061186x.2022.2085730

Cited by 21 publications

(13 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous sequencing studies found secondary mutations in approximately 50% of human EHE, including key secondary variants such as CDKN2A , which can serve as a diagnostic marker for aggressive EHE 26 and is able to drive aggressive tumor behavior in a mouse model of WWTR1::CAMTA1 ‐fused EHE 6 . In our EHE patient, we also observed six secondary somatic variants including DIS3, FANCA, FUBP1, MSH3, ROS1, and SHOC2 , all of which have been linked to poor prognosis in cancer 27–32 . FANCA , MSH3 , and ROS1 mutations were also identified in a previous sequencing study of EHE 26 .…”

Section: Discussionsupporting

confidence: 60%

“…6 In our EHE patient, we also observed six secondary somatic variants including DIS3, FANCA, FUBP1, MSH3, ROS1, and SHOC2, all of which have been linked to poor prognosis in cancer. [27][28][29][30][31][32] FANCA, MSH3, and ROS1 mutations were also identified in a previous sequencing study of EHE. 26 Brain metastasis is very rare in EHE, [33][34][35] so it is possible that these secondary mutations may be responsible for this unusual clinical finding.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Epithelioid hemangioendothelioma (EHE) with WWTR1::TFE3 gene fusion, a novel fusion variant

Li,

Dermawan,

Seavey

et al. 2024

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Epithelioid hemangioendothelioma (EHE) is a rare endothelial sarcoma associated with a high incidence of metastases and for which there are no standard treatment options. Based on disease‐defining mutations, most EHEs are classified into two subtypes: WWTR1::CAMTA1‐fused EHE or YAP1::TFE3‐fused EHE. However, rare non‐canonical fusions have been identified in clinical samples of EHE cases and are challenging to classify. In this study, we report the identification of a novel WWTR1::TFE3 fusion variant in an EHE patient using targeted RNA sequencing. Histologically, the tumor exhibited hybrid morphological characteristics between WWTR1::CAMTA1‐fused EHE and YAP1::TFE3‐fused EHE. In addition to the driver fusion, there were six additional secondary mutations identified, including a loss‐of‐function FANCA mutation. Furthermore, in vitro studies were conducted to investigate the tumorigenic function of the WWTR1::TFE3 fusion protein in NIH3T3 cells and demonstrated that WWTR1::TFE3 promotes colony formation in soft agar. Finally, as the wild‐type WWTR1 protein relies on binding the TEAD family of transcription factors to affect gene transcription, mutation of the WWTR1 domain of the fusion protein to inhibit such binding abrogates the transformative effect of WWTR1::TFE3. Overall, we describe a novel gene fusion in EHE with a hybrid histological appearance between the two major genetic subtypes of EHE. Further cases of this very rare subtype of EHE will need to be identified to fully elucidate the clinical and pathological characteristics of this unusual subtype of EHE.

show abstract

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Epithelioid hemangioendothelioma (EHE) with WWTR1::TFE3 gene fusion, a novel fusion variant

Li,

Dermawan,

Seavey

et al. 2024

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…[ 81 ] To date, ceritinib, brigatinib, cabozantinib, lorlatinib, entrectinib, and repotrectinib have been clinically used to combat drug resistance in NSCLC with ROS1 rearrangement. [ 82 ] Studies have shown that cabozantinib, an inhibitor that simultaneously inhibits nine targets, is effective in patients with ROS1 fusion, especially in patients who are resistant to crizotinib. [ 83 ]…”

Section: Emerging Insights Into Drug Resistance In Lung Cancermentioning

confidence: 99%

Nanomedicine Combats Drug Resistance in Lung Cancer

Zheng,

Song,

Zhu

et al. 2023

Advanced Materials

View full text Add to dashboard Cite

Lung cancer is the second most prevalent cancer and the leading cause of cancer‐related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy and radiotherapy are currently available as treatment methods. However, drug resistance is a significant factor in the failure of lung cancer treatments. Novel therapeutics have been exploited to address complicated resistance mechanisms of lung cancer and the advancement of nanomedicine is extremely promising in terms of overcoming drug resistance. Nanomedicine equipped with multi‐functional and tunable physiochemical properties in alignment with tumor genetic profiles could achieve precise, safe, and effective treatment while minimizing or eradicating drug resistance in cancer. Here, we review the discovered resistance mechanisms for lung cancer chemotherapy, molecular targeted therapy, immunotherapy and radiotherapy, and outline novel strategies for the development of nanomedicine against drug resistance. We focus on engineering design, customized delivery, current challenges and clinical translation of nanomedicine in the application of resistant lung cancer.This article is protected by copyright. All rights reserved

show abstract

“…Previous studies have shown that ROS1 fusions account for 1–2% of all cases of NSCLC [ 88 ]. NSCLC patients with ROS1 fusion have several distinct clinical characteristics: they are typically female, younger (<50 years of age), and never or light smokers [ 111 , 112 , 113 ].…”

Section: Actionable Markers For Treatmentmentioning

confidence: 99%

The Role of Genomics and Proteomics in Lung Cancer Early Detection and Treatment

Abbasian

Ardekani

Sobhani

et al. 2022

Cancers

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer-related death worldwide, with non-small-cell lung cancer (NSCLC) being the primary type. Unfortunately, it is often diagnosed at advanced stages, when therapy leaves patients with a dismal prognosis. Despite the advances in genomics and proteomics in the past decade, leading to progress in developing tools for early diagnosis, targeted therapies have shown promising results; however, the 5-year survival of NSCLC patients is only about 15%. Low-dose computed tomography or chest X-ray are the main types of screening tools. Lung cancer patients without specific, actionable mutations are currently treated with conventional therapies, such as platinum-based chemotherapy; however, resistances and relapses often occur in these patients. More noninvasive, inexpensive, and safer diagnostic methods based on novel biomarkers for NSCLC are of paramount importance. In the current review, we summarize genomic and proteomic biomarkers utilized for the early detection and treatment of NSCLC. We further discuss future opportunities to improve biomarkers for early detection and the effective treatment of NSCLC.

show abstract

ROS1-positive non-small cell lung cancer (NSCLC): biology, diagnostics, therapeutics and resistance

Cited by 21 publications

References 138 publications

Epithelioid hemangioendothelioma (EHE) with WWTR1::TFE3 gene fusion, a novel fusion variant

Epithelioid hemangioendothelioma (EHE) with WWTR1::TFE3 gene fusion, a novel fusion variant

Nanomedicine Combats Drug Resistance in Lung Cancer

The Role of Genomics and Proteomics in Lung Cancer Early Detection and Treatment

Contact Info

Product

Resources

About