Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer

Vasconcellos, Vitor Fiorin de; Marta, Guilherme Nader; Silva, Edina MK da; Góis, Aécio Flávio Teixeira de; Castria, Tiago Biachi De; Riera, Rachel

doi:10.1002/14651858.cd009256.pub3

Cited by 37 publications

(38 citation statements)

References 39 publications

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“…Nowadays, platinum-based chemotherapy remains the cornerstone of routine adjuvant chemotherapy. This approach moderately improves 5-year survival rate, whereas its long-term clinical effectiveness severely impeded by the inherited or acquired resistance to the platinum-based reagents [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

KIAA1522 potentiates TNFα-NFκB signaling to antagonize platinum-based chemotherapy in lung adenocarcinoma

Wang

Jing

Jin

et al. 2020

J Exp Clin Cancer Res

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Background: The platinum-based chemotherapy is the first-line regimen for the treatment of Non-small cell lung cancer (NSCLC). However, the therapeutic efficiency is largely limited by tenacious chemo-insensitivity that results in inferior prognosis in a cohort of patients. It has been known that KIAA1522 is aberrantly expressed and implicated in several types of solid tumors including NSCLC. Nowadays, knowledge about this gene is quite limited. Here, we aimed to identify the role of KIAA1522 in lung adenocarcinomas, and the molecular events that underlie KIAA1522mediated chemoresistance to the platinum. Methods: Immunohistochemistry were used to detect KIAA1522 expression in clinical NSCLC samples. Then, the survival analyses were performed to assess the link between KIAA1522 expression and overall survival or therapeutic outcome. In vivo depletion of KIAA1522 in adenocarcinoma cells were achieved by adeno-associated virusmediated sgRNA/Cre delivery into the conditional Kras G12D /Cas9 expressed mice, which were designated to identify the roles of KIAA1522 in tumorigenesis and/or chemotherapy responses. The effects of KIAA1522 and downstream molecular events were studied by pharmacology in mice model and assays using in vitro cultured cells. The clinical relevance of our findings was examined by data-mining of online datasets from multiple cohorts. Results: The clinical evidences reveal that KIAA1522 independently predicts both the overall survival and the outcome of platinum-based chemotherapy in lung adenocarcinomas. By using a Kras G12D-driven murine lung adenocarcinoma model and performing in vitro assays, we demonstrated that KIAA1522 is a critical positive regulator of lung adenocarcinoma and a modulator of cisplatin response. KIAA1522 potentiates the TNFα-TNFR2-NFκB signaling which in turn intensifies recalcitrance to cisplatin treatment. These results were further manifested by integrative bioinformatic analyses of independent datasets, in which KIAA1522 is tightly associated with the activity of TNFα-NFκB pathway and the cisplatin-resistant gene signatures. More strikingly, overexpression of KIAA1522 counteracts the cisplatin-induced tumor growth arrest in vivo, and this effect can be remarkably diminished by the disruption of NFκB activity.

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Section: Introductionmentioning

confidence: 99%

KIAA1522 potentiates TNFα-NFκB signaling to antagonize platinum-based chemotherapy in lung adenocarcinoma

Wang

Jing

Jin

et al. 2020

J Exp Clin Cancer Res

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“…Non-small cell lung cancer (NSCLC) accounts for ~85% of histological subtypes among all types of lung cancer (3). Chemotherapy is the most commonly used therapeutic regimen for the majority of patients with NSCLC, and significant progress has been achieved with targeted or immunotherapeutic agents for the treatment of NSCLC (4). However, the 5-year survival rate of patients with NSCLC still remains very low (5).…”

Section: Introductionmentioning

confidence: 99%

Combination treatment of gemcitabine and sorafenib exerts a synergistic inhibitory effect on non‑small cell lung cancer in�vitro and in�vivo via the epithelial‑to‑mesenchymal transition process

et al. 2020

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Standard chemotherapy is commonly used in clinical practice for the treatment of non-small cell lung cancer (NSCLC). However, its therapeutic efficacy remains low. Combination therapy for cancer treatment has attracted attention in recent years. The present study aimed to investigate the antitumor effect of the combination treatment with gemcitabine and sorafenib on NSCLC in vitro and in vivo, and to determine its underlying molecular mechanisms. The anti-NSCLC effects of combination therapy were analyzed by flow cytometry analysis, MTT, western blotting, reverse transcription-quantitative PCR, wound healing and Transwell invasion assays. A549 cells subjected to combination treatment with gemcitabine and sorafenib demonstrated a more irregular cellular morphology and lower cell viability compared with the monotherapy groups. Combination of gemcitabine and sorafenib significantly induced cell cycle arrest and apoptosis in A549 cells. Additionally, combination therapy was demonstrated to restrain the migration and invasion of tumor cells by suppressing epithelial-to-mesenchymal transition (EMT) of A549 cells. In vivo analyses confirmed that co-treatment with gemcitabine and sorafenib decreased NSCLC tumor growth and tumor weight in nude mice. Taken together, the results of the present study suggested that combination treatment with gemcitabine and sorafenib exerted a synergistic inhibitory effect on NSCLC in vitro and in vivo via the EMT process.Abbreviations: NSCLC, non-small cell lung cancer; EMT, epithelial-to-mesenchymal transition

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“…Carboplatin is as effective as cisplatin in the treatment of ovarian cancer, but it is better tolerated (16), whereas it shows no clear tolerability benefit over cisplatin in the treatment of lung cancer (17). The third-generation platinum-derived antitumor drug oxaliplatin, which obtained FDA approval in 1996, is mainly used in colorectal cancer in combination therapy (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Cisplatin is more mutagenic than carboplatin or oxaliplatin at equitoxic concentrations

Szikriszt

Póti

Németh

et al. 2020

Preprint

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Platinum-based drugs are a mainstay of cancer chemotherapy. However, their mutagenic effect can increase tumour heterogeneity, contribute to the evolution of treatment resistance, and also induce secondary malignancies. We coupled whole genome sequencing with phenotypic investigations on two cell line models to compare the magnitude and understand the mechanism of mutagenicity of cisplatin, carboplatin and oxaliplatin. Cisplatin induced significantly more base substitution mutations than carboplatin or oxaliplatin when used at equitoxic concentrations on human TK6 or chicken DT40 cells, and also induced the highest number of short insertions and deletions. Assessment through histone H2AX phosphorylation and single cell agarose gel electrophoresis suggested that cisplatin caused more DNA damage than carboplatin or oxaliplatin. The analysis of base substitution spectra revealed that all three tested platinum drugs elicit both a direct mutagenic effect at purine dinucleotides, and an indirect effect of accelerating endogenous mutagenic processes. Whereas the direct mutagenic effect correlated with the level of DNA damage caused, the indirect mutagenic effects were equal. The different mutagenicity and DNA damaging effect of equitoxic platinum drug treatments suggests that DNA damage independent mechanisms significantly contribute to their cytotoxicity. Thus, the comparatively high mutagenicity of cisplatin should be taken into account in the design of chemotherapeutic regimens.

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Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer

Abstract: Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.

Cited by 37 publications

References 39 publications

KIAA1522 potentiates TNFα-NFκB signaling to antagonize platinum-based chemotherapy in lung adenocarcinoma

KIAA1522 potentiates TNFα-NFκB signaling to antagonize platinum-based chemotherapy in lung adenocarcinoma

Combination treatment of gemcitabine and sorafenib exerts a synergistic inhibitory effect on non‑small cell lung cancer in�vitro and in�vivo via the epithelial‑to‑mesenchymal transition process

Cisplatin is more mutagenic than carboplatin or oxaliplatin at equitoxic concentrations

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