Coregulation of pathways in lung cancer patients with EGFR mutation: therapeutic opportunities

Rosell, Rafael; Cardona, Andrés Felipe; Arrieta, Óscar; Aguilar, Andrés; Ito, Masaoki; Pedraz, Carlos; Codony-Servat, Jordi; Santarpía, Mariacarmela

doi:10.1038/s41416-021-01519-2

Cited by 36 publications

(22 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, thirdgeneration EGFR-TKIs still cannot prevent the development of acquired resistance due to persistent mutations in the gene (Lee, 2017;Remon et al, 2018). An increasing number of studies have shown that combining existing small molecule anticancer drugs with EGFR-TKIs can circumvent acquired drug resistance and enhance the antitumor effects of EGFR-TKIs through a bypass signaling mechanism (Rosell et al, 2021). In the present study, we found that the combination of EGFR-TKIs and SAHA is a potential treatment option to reverse the acquired resistance of EGFR-TKIs in NSCLC.…”

Section: Discussionmentioning

confidence: 50%

Combining EGFR-TKI With SAHA Overcomes EGFR-TKI-Acquired Resistance by Reducing the Protective Autophagy in Non-Small Cell Lung Cancer

Cao

Shi

et al. 2022

Front. Chem.

View full text Add to dashboard Cite

Nowadays, lung cancer has the highest mortality worldwide. The emergence of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has greatly improved the survival of patients with non-small cell lung cancer (NSCLC) having EGFR-TKI-sensitive mutations. Unfortunately, acquired resistance happens for most patients. In the present research, we found that EGFR-TKIs (such as gefitinib and osimertinib) can induce autophagy in NSCLC cell lines. Compared with parental sensitive cells, drug-resistant cells have higher autophagy activity. The use of an autophagy inhibitor could enhance the toxicity of gefitinib and osimertinib, which indicates that the enhancement of protective autophagy might be one of the mechanisms of EGFR-TKI resistance in NSCLC. In addition, increased autophagy activity is associated with decreased enhancer of zeste homolog 2 (EZH2) expression. Knockdown of EZH2 or EZH2 inhibitor treatment could lead to increased autophagy in NSCLC cells, indicating that EZH2 is a negative regulator of autophagy. We revealed that the increase in autophagy caused by the reduction of EZH2 was reversed in vitro and in vivo when combining gefitinib or osimertinib with suberoylanilide hydroxamic acid (SAHA), a broad-spectrum histone deacetylase inhibitor (HDACi). In conclusion, our results indicated that the combination of EGFR-TKIs and SAHA may be a new strategy to overcome EGFR-TKIs acquired resistance.

show abstract

Section: Discussionmentioning

confidence: 50%

Combining EGFR-TKI With SAHA Overcomes EGFR-TKI-Acquired Resistance by Reducing the Protective Autophagy in Non-Small Cell Lung Cancer

Cao

Shi

et al. 2022

Front. Chem.

View full text Add to dashboard Cite

show abstract

“…The morbidity and mortality of LADC are increasing year-on-year due to early tumor recurrence, enhanced resistance to chemoradiotherapy, and rapid progression of the disease (62). Chemotherapy targeting mutated tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) has recently become the main strategic treatment for LADC patients, such as in gefitinib, erlotinib, and afatinib (63). Joseph et al (43) discovered that SUMO-activating enzyme subunit 1 (SAE1) and circCCDC66 were highly expressed in LADC.…”

Section: Circccdc66 and Lung Cancermentioning

confidence: 99%

CircCCDC66: Emerging roles and potential clinical values in malignant tumors

et al. 2023

View full text Add to dashboard Cite

Circular RNAs (circRNAs) are endogenous non-coding RNAs (ncRNAs) with a closed-loop structure. In recent years, circRNAs have become the focus of much research into RNA. CircCCDC66 has been identified as a novel oncogenic circRNA and is up-regulated in a variety of malignant tumors including thyroid cancer, non-small cell carcinoma, gastric cancer, colorectal cancer, renal cancer, cervical cancer, glioma, and osteosarcoma. It mediates cancer progression by regulating epigenetic modifications, variable splicing, transcription, and protein translation. The oncogenicity of circCCDC66 suppresses or promotes the expression of related genes mainly through direct or indirect pathways. This finding suggests that circCCDC66 is a biomarker for cancer diagnosis, prognosis assessment and treatment. However, there is no review on the relationship between circCCDC66 and cancers. Thus, the expression, biological functions, and regulatory mechanisms of circCCDC66 in malignant tumor and non-tumor diseases are summarized. The clinical value and prognostic significance of circCCDC66 are also evaluated, which can provide insights helpful to those exploring new strategies for the early diagnosis and targeted treatment of malignancies.

show abstract

“…As genetic sequencing techniques are increasingly available, oncogenic driver mutations and other genomic alterations are frequently identified, guiding cancer therapy (4). In case of women of reproductive age, there are higher probabilities for harbored epidermal growth factor receptor (EGFR) mutations (5,6).…”

Section: Introductionmentioning

confidence: 99%

Case report: Osimertinib administration during pregnancy in a woman with advanced EGFR-mutant non-small cell lung cancer

et al. 2023

Self Cite

View full text Add to dashboard Cite

Lung cancer (LC) is one of the most common causes of death worldwide. The identification of oncogene-addicted driving mutations suitable for targeted therapy has improved clinical outcomes in advanced diseases. Clinical trials, on the other hand, rarely involve vulnerable groups such as pregnant women. We report a 37-year-old woman with advanced non-small cell lung cancer (NSCLC) harboring an exon 19 deletion of EGFR treated with afatinib. After the initial treatment, the patient achieved a complete response and had an unplanned pregnancy. Targeted therapy was withheld during the first trimester and resumed with osimertinib in the second trimester in which the patient developed oligohydramnios and intrauterine growth restriction (IUGR) of the baby. Osimertinib was delayed at two different times during the third trimester with complete resolution of the oligohydramnios. The baby was born at 37.3 weeks of gestation (WOG) with no signs of congenital disorders. After delivery, the mother restarted osimertinib and maintained a complete response. This case suggests that osimertinib could be an acceptable option for tumor control during pregnancy in EGFR-mutant NSCLC. This information do not replace current recommendations for avoiding pregnancy and promoting contraceptive usage in patients receiving any cancer therapy.

show abstract

Coregulation of pathways in lung cancer patients with EGFR mutation: therapeutic opportunities

Cited by 36 publications

References 91 publications

Combining EGFR-TKI With SAHA Overcomes EGFR-TKI-Acquired Resistance by Reducing the Protective Autophagy in Non-Small Cell Lung Cancer

Combining EGFR-TKI With SAHA Overcomes EGFR-TKI-Acquired Resistance by Reducing the Protective Autophagy in Non-Small Cell Lung Cancer

CircCCDC66: Emerging roles and potential clinical values in malignant tumors

Case report: Osimertinib administration during pregnancy in a woman with advanced EGFR-mutant non-small cell lung cancer

Contact Info

Product

Resources

About