Non-small cell lung cancer recurrence following surgery and perioperative chemotherapy: Comparison of two chemotherapy regimens (IFCT-0702: A randomized phase 3 final results study)

Moro-Sibilot, Denis; Audigier-Valette, Clarisse; Merle, P.; Quoix, Élisabeth; Souquet, Pierre-Jean; Chouaïd, C.; Molinier, Olivier; Bennouna, Jaafar; Lavolé, A.; Toffart, Anne‐Claire; Langlais, Alexandra; Morin, Franck; Zalcman, Gérard

doi:10.1016/j.lungcan.2015.05.016

Cited by 10 publications

(5 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lung cancer, classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) subtypes, is the first leading cause of mortality with the five-year survival rate as low as 8-15%. Lung adenocarcinoma is the most common form of NSCLC, which represents about 50% of lung cancer cases 1 , 2 . Epidermal growth factor receptor (EGFR) is a predominant driver oncogene and therapeutic target mutated in higher frequencies at about 60% of lung adenocarcinoma in East Asian countries, than at 35% in Western Caucasian population.…”

Section: Introductionmentioning

confidence: 99%

Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase

et al. 2018

View full text Add to dashboard Cite

How to improve the efficacy and reverse the resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, remains a major challenge in the targeted therapy of lung adenocarcinoma with EGFR-activating mutation. Phosphoglycerate dehydrogenase (PHGDH) is the key enzyme of de novo serine biosynthesis over-expressed in various types of cancer including lung cancer. Elevated PHGDH expression is correlated with a worse overall survival in clinical lung adenocarcinoma patients. Here we investigated the role of PHGDH in lung adenocarcinoma with the acquisition of resistance to erlotinib.Methods: The necessary genes required for the acquired erlotinib resistance in lung adenocarcinoma cells were screened out by RNA-Seq analysis. Then the protein and mRNA levels of PHGDH were confirmed by immunoblotting and qRT-PCR in the erlotinib resistant cells. The effects of PHGDH inhibition or overexpression on erlotinib resistance were examined using cell culture and tumor xenograft mouse models respectively. To explore mechanism, the ROS level and DNA damage marker, γH2AX, were tested by DCFH-DA staining and immunofluorescence after PHGDH inhibition.Results: We found that PHGDH level was significantly increased in the lung adenocarcinoma PC9ER4 and HCC827ER9 cells that acquired resistance to erlotinib. Perturbation of PHGDH by siPHGDH transfection or NCT-503, a small molecular PHGDH inhibitor, synergistically augmented the tumoricidal effect and restored sensitivity to erlotinib in cell lines and xenografts. Over-expression of PHGDH caused xenografts resistant to erlotinib. Furthermore, multiple DNA damage repair pathways related genes were changed by PHGDH depletion specifically in erlotinib resistant cells. ROS stress and DNA damage marker γH2AX were enhanced by siPHGDH and NCT-503, which was reversed by NAC.Conclusion: Our study indicated that PHGDH inhibition has potential therapeutic value in lung adenocarcinoma with the acquired resistance to EGFR-TKIs.

show abstract

Section: Introductionmentioning

confidence: 99%

Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase

et al. 2018

View full text Add to dashboard Cite

show abstract

“…However, the influence of other clinical factors relevant for this choice is unknown. To the best of our knowledge, there is only one trial dealing with chemotherapy in patients relapsing after chemotherapy [31]. This trial tends to support this attitude and showed a nonsignificant increase in progression-free survival and overall survival with doublet chemotherapy.…”

mentioning

confidence: 92%

Optimising treatment for post-operative lung cancer recurrence

2016

View full text Add to dashboard Cite

@ERSpublicationsThe second lung resection is a valuable option for post-operative lung cancer recurrence http://ow.ly/U8z3cSurgical treatment offers the best chances for long-term survival in patients with primary nonsmall cell lung cancer (NSCLC). However, long-term survival after surgery remains less than 50%, mostly due to a 30-77% rate of tumour recurrence. Unlike the distant type of recurrence that is treated nonsurgically in the vast majority of patients, local or loco-regional recurrence, which occurs in 4.6-24% of patients after complete resection (∼80% of cases in the first 2 years) [1], raises several concerns related to the optimal therapeutic approach.Unfortunately, literature data are not always helpful in practice. For example, 5-year loco-regional recurrence rates are between 15 and 38.5% [2], and the incidence of local recurrence in early-stage lung cancer of 10-15% [3], or a mean disease-free interval of 14.1-19.8 months, that is similar to distant recurrent disease [4]. Failure to demonstrate the advantage of complete lymphadenectomy over nodal sampling in terms of local recurrence or survival in patients operated for T1-2, N0 or T1-2, N1 disease, makes the clinical approach more complex [5]. Moreover, the impact of intensified follow-up on overall survival or local recurrence detection could not be clearly demonstrated. In ∼50-67% of patients, recurrence will appear before a scheduled control because of the onset of symptoms [6].Finally, switching to seventh edition of the TNM (tumour, node, metastasis) staging system automatically led to the stage migration, reaching 21% in some studies. The only study of the role of computed tomography (CT) in post-operative recurrence detection demonstrated a high negative predictive value of 95%, but a positive predictive value of only 53% (94% sensitivity and 87% specificity) [7]. For positron emission tomography, although it is more sensitive than CT in detecting recurrent tumours (97-100%), variations of the cut-off values for the standardised uptake value (⩾4.5-⩾10) make its clinical application difficult, together with its specificity (62-100%) that is lower than for CT.The role of prognostic factors after surgery is more evidence-based, owing to awareness of the poor 5-year survival of patients in stages IA and IB (73% and 58%, respectively). This also applies to the high recurrence rate in patients with stage I after complete resection (25-50%) [8]. The results of these studies really helped to identify patients who would probably benefit from adjuvant therapy.Among tumour markers, although increased serum concentrations of carcinoembryonic antigen (CEA) are rare (17%), persistently high post-operative CEA levels were found to be a strong indicator of poor prognosis. In 55-70% of patients with CEA values of 5-10 ng·mL , an early recurrence will develop [9].Of the many analysed clinical and pathological prognostic factors, vascular invasion, lymphatic vessel and visceral pleural invasion have been identified as clearly unfavourable in terms of surviv...

show abstract

“…Lung cancer is a leading cause of cancer mortality worldwide, more than 85% of which is non-small cell lung cancer (NSCLC). Lung adenocarcinoma is the major form of NSCLC, which represents about 50% of lung cancer [ 1 ]. Epidermal growth factor receptor (EGFR) mutation is a main contributing factor of lung adenocarcinoma (LUAD) in east Asian countries (about 60% of lung adenocarcinoma) [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology

Bing

Cheng²,

Shi

et al. 2018

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundChinese traditional herbal medicine Fuzhengkangai (FZKA) formulation combination with gefitinib can overcome drug resistance and improve the prognosis of lung adenocarcinoma patients. However, the pharmacological and molecular mechanisms underlying the active ingredients, potential targets, and overcome drug resistance of the drug are still unclear. Therefore, it is necessary to explore the molecular mechanism of FZKA.MethodsA systems pharmacology and bioinformatics-based approach was employed to investigate the molecular pathogenesis of EGFR-TKI resistance with clinically effective herb formula. The differential gene expressions between EGFR-TKI sensitive and resistance cell lines were calculated and used to find overlap from targets as core targets. The prognosis of core targets was validated from the cancer genome atlas (TCGA) database by Cox regression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment is applied to analysis core targets for revealing mechanism in biology.ResultsThe results showed that 35 active compounds of FZKA can interact with eight core targets proteins (ADRB2, BCL2, CDKN1A, HTR2C, KCNMA1, PLA2G4A, PRKCA and LYZ). The risk score of them were associated with overall survival and relapse free time (HR = 6.604, 95% CI: 2.314–18.850; HR = 5.132, 95% CI: 1.531–17.220). The pathway enrichment suggested that they involved in EGFR-TKI resistance and non-small cell lung cancer pathways, which directly affect EGFR-TKI resistance. The molecular docking showed that licochalcone a and beta-sitosterol can closely bind two targets (BCL2 and PRKCA) that involved in EGFR-TKI resistance pathway.ConclusionsThis study provided a workflow for understanding mechanism of CHM for against drug resistance.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2347-x) contains supplementary material, which is available to authorized users.

show abstract

Non-small cell lung cancer recurrence following surgery and perioperative chemotherapy: Comparison of two chemotherapy regimens (IFCT-0702: A randomized phase 3 final results study)

Cited by 10 publications

References 27 publications

Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase

Overcoming erlotinib resistance in EGFR mutation-positive lung adenocarcinomas through repression of phosphoglycerate dehydrogenase

Optimising treatment for post-operative lung cancer recurrence

Investigate the mechanisms of Chinese medicine Fuzhengkangai towards EGFR mutation-positive lung adenocarcinomas by network pharmacology

Contact Info

Product

Resources

About