Modulation of Signaling Enhances the Efficacy of the Combination of Satraplatin and Erlotinib

Avan, Abolfazl; Adema, Auke D.; Hoebe, Eveline K.; Huijts, Charlotte M.; Avan, Amir; Veal, Gareth J.; Ruijtenbeek, Rob; Wosikowski, Katja; Peters, Godefridus J.

doi:10.2174/1389450115666141107110321

Cited by 7 publications

(5 citation statements)

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“…although, further studies are needed to understand the mechanisms of TLRs and novel TLR inhibitors in CRC. Moreover, the application of different cytotoxic agents is related with enhanced toxicity, indicating the need for assessing natural compound, such as curcumin or crocin (Avan et al, ; Bahrami, Amerizadeh, et al, ; Bahrami, Amerizadeh, et al, ; Bahrami, Hassanian, et al, ; Bahrami, Hassanian, et al, ; Bahrami, Hesari, et al ; Hosseini et al, ; Rahmani et al, ; Vatandoost et al, ). Moreover parallel targeting of other pathway (e.g., PI3K/Akt, Wnt/b‐catenin, RAS/MAP pathways) are warranted to overcome cell resistance or prevent the possible feedback loop between these pathways in colorectal cancer.…”

Section: Resultsmentioning

confidence: 99%

Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer

Moradi‐Marjaneh

Hassanian

Fiuji

et al. 2018

Journal Cellular Physiology

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Toll like receptor (TLR) signaling is involved in activating innate and adaptive immune responses and plays a critical role in inflammation-induced diseases such as colorectal cancer (CRC). Dysregulation of this signaling pathway can result in disturbance of epithelial layer hemostasis, chronic inflammatory, excessive repair responses, and development of CRC. There is now substantial evidence for the benefit of targeting of this pathway in cancer treatment, and several agents have been approved, such as BCG (Bacillus Calmette Guérin), MPL (monophosphoryl lipid A) and imiquimod. This review summarizes the current knowledge about the different functions of TLRs on tumor cells and their application in cancer therapy with particular emphasis on recent preclinical and clinical research in treatment of CRC.

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Section: Resultsmentioning

confidence: 99%

Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer

Moradi‐Marjaneh

Hassanian

Fiuji

et al. 2018

Journal Cellular Physiology

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“…Other TKIs have been known in vitro to synergize with chemotherapy, such as EGFR-inhibitors with platinum doublet chemotherapy[35-38], whereas clinical trials showed no substantial benefit when combining both drugs. Combinations of cisplatin with EGFR-TKIs, have been investigated extensively, both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

“…In wild-type EGFR (WT-EGFR) NSCLC cell lines, cisplatin may upregulate phosphorylated EGFR, thus sensitizing these cells to erlotinib; However, in NSCLC cell lines with sensitizing EGFR mutations, combining cisplatin with erlotinib treatment was found to be antagonistic[36]. Other studies showed that platinum analogs in combination with erlotinib led to synergistic cell death in EGFR-mutant NSCLC cell lines and xenografts[37,38]. Possible mechanisms for this synergy are a decrease in hypoxia-inducible factor 1α (HIF1α), a decrease in c-Myc or cell cycle effects[37], while also platinum-adduct formation by cisplatin was increased[38].…”

Section: Discussionmentioning

confidence: 99%

“…Other studies showed that platinum analogs in combination with erlotinib led to synergistic cell death in EGFR-mutant NSCLC cell lines and xenografts[37,38]. Possible mechanisms for this synergy are a decrease in hypoxia-inducible factor 1α (HIF1α), a decrease in c-Myc or cell cycle effects[37], while also platinum-adduct formation by cisplatin was increased[38]. However, several clinical trials[8,9,39-41] combining cisplatin with EGFR-TKIs show no benefit in EGFR-WT or in EGFR-mutant patients.…”

Section: Discussionmentioning

confidence: 99%

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Better to be alone than in bad company: The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

Steen¹,

Deben²,

Deschoolmeester³

et al. 2016

WJCO

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AIMTo investigate the potential benefit of combining the cMET inhibitor crizotinib and cisplatin we performed in vitro combination studies.METHODSWe tested three different treatment schemes in four non-small cell lung cancer (NSCLC) cell lines with a different cMET/epidermal growth factor receptor genetic background by means of the sulforhodamine B assay and performed analysis with Calcusyn.RESULTSAll treatment schemes showed an antagonistic effect in all cell lines, independent of the cMET status. Despite their different genetic backgrounds, all cell lines (EBC-1, HCC827, H1975 and LUDLU-1) showed antagonistic combination indexes ranging from 1.3-2.7. These results were independent of the treatment schedule.CONCLUSIONThese results discourage further efforts to combine cMET inhibition with cisplatin chemotherapy in NSCLC.

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“…Both in experimental systems and in patients it has been demonstrated that inhibition of AKT or EGFR can neutralize the AKT activation and enhance efficacy of standard drugs. For instance in several NSCLC models erlotinib increased the efficacy of pemetrexed [155] , while inhibition of AKT with perifosine enhanced the efficacy of the platinum analog satraplatin [156] . MK2206 enhanced the effect of radiation alone [157] or in combination with gemcitabine and radiation (El-Naggar, unpublished results).…”

Section: Future Directionsmentioning

confidence: 99%

Resistance to epidermal growth factor receptor inhibition in non-small cell lung cancer

Steen¹,

Giovannetti²,

Carbone³

et al. 2018

CDR

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Aberrant activation of the epidermal growth factor receptor (EGFR) is a driving force for cancer growth in a subgroup of non-small cell lung cancer patients. These patients can be identified by the presence of activating EGFR mutations. Currently three generations of EGFR-tyrosine kinase inhibitors (TKIs) have been approved by the Food and Drug Administration and European Medicine Agency. This paper reviews the structure of EGFR and the downstream signaling pathways of EGFR and describes the mechanisms of intrinsic and acquired resistance against EGFR-TKIs. These mechanisms include secondary or tertiary mutations in EGFR, the activation of bypassing signaling pathways or a histological transformation to small cell lung cancer. Moreover, drug efflux transporters will affect the cellular accumulation of EGFR-TKIs and penetration of the first generation of EGFR-TKI into the brain. Lysosomal sequestration of some EGFR-TKIs may also prevent the drugs to reach their target. In conclusion, resistance to EGFR-TKIs is multifactorial, including primary and acquired mutations in the EGFR gene, activation of bypassing pathways and limited uptake of drugs in the cells or target tissues. More pharmacological studies are needed in order to develop new specific compounds targeted to overcome new resistance mechanisms in order to enable a personalized treatment approach.

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Modulation of Signaling Enhances the Efficacy of the Combination of Satraplatin and Erlotinib

Abstract: Erlotinib enhanced the effects of JM118, even in cells with mutations in Ras. The mechanism of synergy involved a combination of effects on platinum-DNA adduct formation, cell cycle distribution and signaling.

Cited by 7 publications

References 45 publications

Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer

Toll like receptor signaling pathway as a potential therapeutic target in colorectal cancer

Better to be alone than in bad company: The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

Resistance to epidermal growth factor receptor inhibition in non-small cell lung cancer

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