YES1 Drives Lung Cancer Growth and Progression and Predicts Sensitivity to Dasatinib

Garmendia, Irati; Pajares, María J.; Hermida-Prado, Francisco; Ajona, Daniel; Bértolo, Cristina; Sainz, Cristina; Lavin, A. Cotero; Remírez, Ana; Valencia, Karmele; Moreno, Haritz; Ferrer, Irene; Behrens, Carmen; Cuadrado, Myriam; Paz‐Ares, Luis; Bustelo, Xosé R.; Gil‐Bazo, Ignacio; Alameda, Daniel; Lecanda, Fernando; Calvo, Alfonso; Felip, Enriqueta; Sanchez-Cespedes, Montse; Wistuba, Ignacio I.; Granda-Díaz, Rocío; Rodrigo, Juan P.; García-Pedrero, Juana M.; Pı́o, Rubén; Montuenga, Luis M.; Agorreta, Jackeline

doi:10.1164/rccm.201807-1292oc

Cited by 52 publications

(52 citation statements)

References 45 publications

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“…The characterization of new genetic alterations is essential to assign effective personalized therapies in NSCLC; furthermore, finding stratification biomarkers is essential for successful personalized therapies. In this direction, Garmendia et al showed that molecular alterations of Yes can be found in a significant subset of patients with lung cancer and they demonstrated an association between these alterations and prognosis using Yes status as predictive biomarker [76]. Also, the same authors demonstrated that stable Yes overexpression in human NSCLC cell lines induced proliferation, increased tumor growth and metastasis, but conversely, genetic depletion of Yes using siRNAs or CRISPR/Cas9 in human NSCLC cell lines reduced proliferation, survival, and invasion in vitro and tumor growth and lung metastatic growth.…”

Section: Lung Cancermentioning

confidence: 99%

Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned So Far

Martellucci

Clementi

Sabetta

et al. 2020

Cancers

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Src is the prototypal member of Src Family tyrosine Kinases (SFKs), a large non-receptor kinase class that controls multiple signaling pathways in animal cells. SFKs activation is necessary for the mitogenic signal from many growth factors, but also for the acquisition of migratory and invasive phenotype. Indeed, oncogenic activation of SFKs has been demonstrated to play an important role in solid cancers; promoting tumor growth and formation of distant metastases. Several drugs targeting SFKs have been developed and tested in preclinical models and many of them have successfully reached clinical use in hematologic cancers. Although in solid tumors SFKs inhibitors have consistently confirmed their ability in blocking cancer cell progression in several experimental models; their utilization in clinical trials has unveiled unexpected complications against an effective utilization in patients. In this review, we summarize basic molecular mechanisms involving SFKs in cancer spreading and metastasization; and discuss preclinical and clinical data highlighting the main challenges for their future application as therapeutic targets in solid cancer progression

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Section: Lung Cancermentioning

confidence: 99%

Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned So Far

Martellucci

Clementi

Sabetta

et al. 2020

Cancers

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“…Other well-characterized oncogenes also present in the EPHA-ephrin signaling pathway include TIAM, YES1, and HRAS (Yang et al 2015;Dotto and Rustgi 2016;Garmendia et al 2019). MYH10, the only pathway member in our cohort with alterations in both single-nucleotide variation (SNV) and copy-number variation (CNV), has been identified as an important hub in other quantitative analyses and plays an important role in cancer migration and invasion (Wang et al 2018;Guo et al 2019;Li et al 2019).…”

Section: Discussionmentioning

confidence: 94%

Functional genomic analysis identifies drug targetable pathways in invasive and metastatic cutaneous squamous cell carcinoma

Anderson

McClanahan

Jacobs

et al. 2020

Cold Spring Harb Mol Case Stud

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Although cutaneous squamous cell carcinoma (cSCC) is treatable in the majority of cases, deadly invasive and metastatic cases do occur. To date there are neither reliable predictive biomarkers of disease progression nor FDA-approved targeted therapies as standard of care. To address these issues, we screened patient-derived primary cultured cells from invasive/metastatic cSCC with 107 small-molecule inhibitors. In-house bioinformatics tools were used to cross-analyze drug responses and DNA mutations in tumors detected by whole-exome sequencing (WES). Aberrations in molecular pathways with evidence of potential drug targets were identified, including the Eph-ephrin and neutrophil degranulation signaling pathways. Using a screening panel of siRNAs, we identified EPHA6 and EPHA7 as targets within the Eph-ephrin pathway responsible for mitigating decreased cell viability. These studies form a plausible foundation for detecting biomarkers of high-risk progressive disease applicable in dermatopathology and for patient-specific therapeutic options for invasive/metastatic cSCC.

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“…YES1 amplification has been found in 15% of lung adenocarcinoma and 25% of lung squamous cell carcinoma patients, and YES1 expression was reported to be related to a shorter OS in NSCLC patients 22 . Garmendia et al 23 . demonstrated that YES1 amplification induces tumor growth as an oncogenic driver alteration in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…Few cases of primary resistance to afatinib for patients harboring EGFR exon 21 L858R missense mutation have been reported and here we present the first case with concurrent alterations of EGFR exon 21 L858R missense mutation and YES1 amplification. Garmendia et al 23 . demonstrated that YES1 amplification presented a high sensitivity to dasatinib, an SFK inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Role of YES1 amplification in EGFR mutation‐positive non‐small cell lung cancer: Primary resistance to afatinib in a patient

2020

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Epidermal growth factor receptor (EGFR) mutation‐positive non‐small cell lung cancer (NSCLC) patients benefit from EGFR tyrosine kinase inhibitors (TKIs), while some patients demonstrate a resistance to EGFR‐TKIs. In the case reported here, the NSCLC patient harboring an EGFR‐sensitive mutation and YES1 amplification was treated with afatinib as first‐line therapy, but was found to have progressive disease four weeks later. During subsequent chemotherapy, this patient's disease progressed rapidly. Mechanisms of primary resistance to EGFR‐TKIs remain unclear. This case suggested that YES1 amplification might be associated with primary resistance to EGFR‐TKIs and YES1 amplification might be a negative predictor of EGFR‐TKI treatment in NSCLC patients harboring EGFR sensitive mutations.

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YES1 Drives Lung Cancer Growth and Progression and Predicts Sensitivity to Dasatinib

Cited by 52 publications

References 45 publications

Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned So Far

Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned So Far

Functional genomic analysis identifies drug targetable pathways in invasive and metastatic cutaneous squamous cell carcinoma

Role of YES1 amplification in EGFR mutation‐positive non‐small cell lung cancer: Primary resistance to afatinib in a patient

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