Treatment of choice for patients with EGFR mutation–positive non-small cell lung carcinoma presenting with choroidal metastases: radiotherapy or TKIs?

Maskell, Daniel; Geropantas, K.; Kouroupis, Michael; Glenn, A.; Ajithkumar, TV

doi:10.1016/j.jcjo.2016.09.010

Cited by 13 publications

(5 citation statements)

References 10 publications

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“…IR plays a crucial role in cancer treatment; however, radio-resistance leads to distant metastases in patients with radiotherapy (46). Accumulated evidence has demonstrated the important role of EMT in metastasis (47).…”

Section: Discussionmentioning

confidence: 99%

RAC1 Involves in the Radioresistance by Mediating Epithelial-Mesenchymal Transition in Lung Cancer

Tan

Wang

et al. 2020

Front. Oncol.

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Radiation therapy is a common and acceptable approach for lung cancer. Although the benefit of ionizing radiation (IR) is well-established, cancer cells can still survive via pro-survival and metastasis signaling pathways. Ras related C3 botulinum toxin substrate1 (RAC1), a member of Rho family GTPases, plays important roles in cell migration and survival. In the present study, we investigated the effects of RAC1 on the survival of lung cancer cells treated with irradiation. The results showed RAC1 is overexpressed in lung cancer cells and promoted cell proliferation and survival. Furthermore, IR induced RAC1 expression and activity via the activation of PI3K/AKT signaling pathway, and then enhancing cell proliferation, survival, migration and metastasis and increasing levels of epithelial-to-mesenchymal transition (EMT) markers, which facilitated the cell survival and invasive phenotypes. In addition, overexpression of RAC1 attenuated the efficacy of irradiation, while inhibition of RAC1 enhanced sensitivity of irradiation in xenograft tumors in vivo. Collectively, we further found that RAC1 enhanced radioresistance by promoting EMT via targeting the PAK1-LIMK1-Cofilins signaling in lung cancer. Our finding provides the evidences to explore RAC1 as a therapeutic target for radioresistant lung cancer cells.

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Section: Discussionmentioning

confidence: 99%

RAC1 Involves in the Radioresistance by Mediating Epithelial-Mesenchymal Transition in Lung Cancer

Tan

Wang

et al. 2020

Front. Oncol.

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“…Specifically, in the case of EGFR-mutated NSCLC, treatment with first generation and second generation EGFR-TKIs has shown improved efficacy and survival compared to treatment with cytotoxic chemotherapy, including objective and sustained responses in cases with choroidal metastases. 9 , 10 , 11 However, in some cases, patients developed a T790 M mutation in EGFR that made them resistant to treatment with first and second generation EGFR-TKIs. Osimertinib, an oral, third-generation, irreversible EGFR-TKI selectively inhibits both EGFR-TKI–sensitizing and EGFR T790 M resistance mutations and has been shown to have improved overall survival over first generation EGFR-TKIs and improved efficacy in the CNS.…”

Section: Discussionmentioning

confidence: 99%

“…Tyrosine kinase inhibitors (TKIs) targeting the EGFR pathway have become the gold standard of treatment for EGFR-mutated NSCLC. First and second generation EGFR-TKIs, such as gefitinib, erlotinib, or afatinib, have shown efficacy in treating choroidal metastasis, 9 , 10 , 11 but an EGFR T790 M resistance mutation can occur that limits the systemic efficacy of these treatments. 12 Osimertinib is an oral, third-generation, irreversible EGFR-TKI that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790 M resistance mutations and has been shown to have improved overall survival over first generation EGFR-TKIs in previously untreated advanced stage NSCLC patients, as well as improved efficacy in the CNS.…”

Section: Introductionmentioning

confidence: 99%

Successful response to first-line treatment with osimertinib for choroidal metastasis from EGFR-mutated non-small-cell lung cancer

Field

Boldt

Hejleh

et al. 2022

American Journal of Ophthalmology Case Reports

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“…The efficacy of TKI agents is equivalent to radiation, and the onset of action is shorter. 37 There have also been reports of successful regression of CM and improvement of symptoms as a result of TKI combined with anti-angiogenic therapy, such as intravitreal bevacizumab. 45 , 46 The explanation may be that EGFR and VEGF share a downstream signaling pathway, and when the activity of VEGF is down-regulated by EGFR inhibitors, deactivation of VEGF simultaneously inhibits the autocrine signal of EGFR.…”

Section: Targeted Therapymentioning

confidence: 99%

A Comprehensive Understanding of Choroidal Metastasis from Lung Cancer

Qu¹,

Liu²,

Zhu³

et al. 2021

OTT

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The incidence of lung cancer with intraocular metastasis is low, of which choroidal metastasis is the most painful metastatic lesion. The clinical symptoms resulting from choroidal metastasis from lung cancer easily detected although they are rarely identified prior to the diagnosis of the primary malignancy. The quality of life of patients is inevitably impaired. Some lung cancer patients complain of ocular symptoms as the first manifestation of lung cancer. Early diagnosis and treatment can significantly overcome or delay the visual impairment and improve prognosis. The main therapeutic modalities include systemic and local treatments, while observation is also a treatment option. Currently, the feasibility and effectiveness of various treatment options are controversial worldwide. Herein, we summarize the underlying mechanisms, epidemiology, clinical features, auxiliary examinations, diagnosis, and recent treatment options for intraocular metastases.

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Treatment of choice for patients with EGFR mutation–positive non-small cell lung carcinoma presenting with choroidal metastases: radiotherapy or TKIs?

Cited by 13 publications

References 10 publications

RAC1 Involves in the Radioresistance by Mediating Epithelial-Mesenchymal Transition in Lung Cancer

RAC1 Involves in the Radioresistance by Mediating Epithelial-Mesenchymal Transition in Lung Cancer

Successful response to first-line treatment with osimertinib for choroidal metastasis from EGFR-mutated non-small-cell lung cancer

A Comprehensive Understanding of Choroidal Metastasis from Lung Cancer

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