Synergistic interaction between sunitinib and docetaxel is sequence dependent in human non–small lung cancer with EGFR TKIs-resistant mutation

Pan, Feng; Tian, Jing; Zhang, Xuchao; Zhang, Ying; Pan, Yueyin

doi:10.1007/s00432-011-1009-x

Cited by 14 publications

(12 citation statements)

References 65 publications

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“…For instance, a phase I/II trial in which patients received treatment with erlotinib prior to its combination with TMZ and radiotherapy (RT) showed no benefit when compared to the standard historical treatment [20], whereas another clinical trial assessing a similar combination in which patients where administered erlotinib and TMZ continuosly from the beginning reported a better survival than historical controls [21]. Similarly, recent work in lung cancer cells has also highlighted the importance of drug scheduling when combining TKIs and conventional chemotherapeutic agents [22], [23]. Noteworthy, the timing of administration in combinations of erlotinib or other TKIs leading to G 1 arrest together with radiotherapy in glioma patients should also be carefully considered, since cellular radiosensitivity has also been shown to be cell cycle dependent [24].…”

Section: Discussionmentioning

confidence: 99%

EGFR Inhibition in Glioma Cells Modulates Rho Signaling to Inhibit Cell Motility and Invasion and Cooperates with Temozolomide to Reduce Cell Growth

et al. 2012

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Enforced EGFR activation upon gene amplification and/or mutation is a common hallmark of malignant glioma. Small molecule EGFR tyrosine kinase inhibitors, such as erlotinib (Tarceva), have shown some activity in a subset of glioma patients in recent trials, although the reported data on the cellular basis of glioma cell responsiveness to these compounds have been contradictory. Here we have used a panel of human glioma cell lines, including cells with amplified or mutant EGFR, to further characterize the cellular effects of EGFR inhibition with erlotinib. Dose-response and cellular growth assays indicate that erlotinib reduces cell proliferation in all tested cell lines without inducing cytotoxic effects. Flow cytometric analyses confirm that EGFR inhibition does not induce apoptosis in glioma cells, leading to cell cycle arrest in G1. Interestingly, erlotinib also prevents spontaneous multicellular tumour spheroid growth in U87MG cells and cooperates with sub-optimal doses of temozolomide (TMZ) to reduce multicellular tumour spheroid growth. This cooperation appears to be schedule-dependent, since pre-treatment with erlotinib protects against TMZ-induced cytotoxicity whereas concomitant treatment results in a cooperative effect. Cell cycle arrest in erlotinib-treated cells is associated with an inhibition of ERK and Akt signaling, resulting in cyclin D1 downregulation, an increase in p27kip1 levels and pRB hypophosphorylation. Interestingly, EGFR inhibition also perturbs Rho GTPase signaling and cellular morphology, leading to Rho/ROCK-dependent formation of actin stress fibres and the inhibition of glioma cell motility and invasion.

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Section: Discussionmentioning

confidence: 99%

EGFR Inhibition in Glioma Cells Modulates Rho Signaling to Inhibit Cell Motility and Invasion and Cooperates with Temozolomide to Reduce Cell Growth

et al. 2012

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“…Therefore, the Cab ∼ Doc sequential regimen was less effective. Similar findings of schedule-dependent interactions have been reported by several teams (Ricotti et al, 2003;Pan et al, 2011;Tamatani et al, 2012;Wang et al, 2012;Jiang et al, 2014).…”

Section: Discussionsupporting

confidence: 89%

“…The Cab ∼ Doc sequential schedule was less effective than the Doc ∼ Cab sequential schedule both in vitro and in vivo, which may be explained by the different effects of the two drugs on cell cycle arrest (Pan et al, 2011). As an antimicrotubule agent, Doc stabilizes microtubules during cell division and causes cell cycle arrest in the G2/M phase (Bissery, 1995).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Modeling of Schedule-Dependent Interaction between Docetaxel and Cabozantinib in Human Prostate Cancer Xenograft Models

Chen

et al. 2017

J Pharmacol Exp Ther

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In this work, a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model to quantitatively describe the antitumor activity of docetaxel (Doc) and cabozantinib (Cab) under monotherapy, concurrent therapy, interval therapy, and different sequential therapy in mouse xenograft models of castration-resistant prostate cancer was developed and evaluated. The pharmacokinetics (PK) of Doc and Cab when administered separately and simultaneously were investigated in nude mice, and PD study was conducted in tumor-bearing mice treated with different dosing schedules. The PK interaction between Doc and Cab was expressed by adding the effect of Cab on the clearance of Doc in the PK model. And the PD interaction between the two drugs was demonstrated by the developed PK/PD model through the combination index "" Our results showed that the concurrent therapy and Doc followed by Cab (Doc ∼ Cab) sequential therapy exhibited better tumor inhibitory efficacy than monotherapy. The Cab followed by Doc (Cab ∼ Doc) sequential schedule was less effective than monotherapy, and the interval therapy did not enhance the antitumor efficacy compared with the concurrent therapy. The parameter φ estimated from the PK/PD model quantitatively characterized the action between Doc and Cab. There was no significant PD interaction between Doc and Cab in both the concurrent schedule and the interval schedule, whereas the effect of the two drugs in the "Doc ∼ Cab" and "Cab ∼ Doc" sequential schedule was synergistic and antagonistic, respectively. The proposed model properly described the antitumor effects of Doc and Cab under different treatment schedules and could be used for dose optimization through model-based simulation.

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“…However, a cell cycle arrest in G 2 -phase phase was described in breast, testicular, head, and neck cell lines [34, 35]. In our study, the treatment of cells with sunitinib malate leads to an accumulation of cells in G 0 /G 1 -phase, an effect that was reported on A549 human non-small-cell lung cancer cells [27]. Moreover, for both drugs in isolation, we obtained an increase percentage of cells in sub-G 0 /G 1 -fraction in the three cell lines, suggesting that both agents induce apoptosis.…”

Section: Discussionsupporting

confidence: 50%

“…Concerning sunitinib malate, its effect was already reported on 5637 [23], TCC-SUP, HTB5, HTB9, T24, UMUC14, SW1710, and J82 urinary bladder-cancer cell lines [24]. Comparable results were reported for other neoplastic cells, such as medullary and papillary thyroid [25], pancreatic adenocarcinoma [26], and non-small-lung cancer cell lines [27]. Also in in vivo studies, sunitinib malate was effective in mouse with small cell lung cancer [28] and in a mouse orthotopic urinary bladder tumor model [29].…”

Section: Discussionmentioning

confidence: 92%

Synergistic Effect between Cisplatin and Sunitinib Malate on Human Urinary Bladder-Cancer Cell Lines

Arantes‐Rodrigues

Pinto‐Leite

Gonçalves

et al. 2013

BioMed Research International

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The aim of this paper is to analyse sunitinib malate in vitro ability to enhance cisplatin cytotoxicity in T24, 5637, and HT1376 human urinary bladder-cancer cell lines. Cells were treated with cisplatin (3, 6, 13, and 18 μM) and sunitinib malate (1, 2, 4, 6, and 20 μM), either in isolation or combined, over the course of 72 hours. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, acridine orange, and monodansylcadaverine staining and flow cytometry were performed. The combination index (CI) was calculated based on the Chou and Talalay method. In isolation, cisplatin and sunitinib malate statistically (P < 0.05) decrease cell viability in all cell lines in a dose-dependent manner, with the presence of autophagic vacuoles. A cell cycle arrest in early S-phase and in G0/G1-phase was also found after exposure to cisplatin and sunitinib malate, in isolation, respectively. Treatment of urinary bladder-cancer cells with a combination of cisplatin and sunitinib malate showed a synergistic effect (CI < 1). Autophagy and apoptosis studies showed a greater incidence when the combined treatment was put into use. This hints at the possibility of a new combined therapeutic approach. If confirmed in vivo, this conjugation may provide a means of new perspectives in muscle-invasive urinary bladder cancer treatment.

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Synergistic interaction between sunitinib and docetaxel is sequence dependent in human non–small lung cancer with EGFR TKIs-resistant mutation

Abstract: Sunitinib as a single agent exhibits anti-proliferative effects in vitro in NSCLC cell lines with EGFR T790M and K-ras mutations but the sequential administration of docetaxel followed by sunitinib is superior to sunitinib followed by docetaxel and concurrent administration.

Cited by 14 publications

References 65 publications

EGFR Inhibition in Glioma Cells Modulates Rho Signaling to Inhibit Cell Motility and Invasion and Cooperates with Temozolomide to Reduce Cell Growth

EGFR Inhibition in Glioma Cells Modulates Rho Signaling to Inhibit Cell Motility and Invasion and Cooperates with Temozolomide to Reduce Cell Growth

Pharmacokinetic/Pharmacodynamic Modeling of Schedule-Dependent Interaction between Docetaxel and Cabozantinib in Human Prostate Cancer Xenograft Models

Synergistic Effect between Cisplatin and Sunitinib Malate on Human Urinary Bladder-Cancer Cell Lines

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