Chronopharmacology and Mechanism of Antitumor Effect of Erlotinib in Lewis Tumor-Bearing Mice

Wang, Peipei; An, Fengmei; Zhuang, Xun; Liu, Jiao; Zhao, Liang; Zhang, Bin; Liu, Liang; Lin, Pingping; Li, Mingchun

doi:10.1371/journal.pone.0101720

Cited by 9 publications

(8 citation statements)

References 31 publications

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“…To test if there is a causal effect of the R and NR bacteria on treatment outcomes, we tested their impact on tumor growth in a murine lung cancer model [32]. As examples of the R-enriched bacteria, B. ovatus and B. xylanisolvens were chosen due to their relatively high significance in the species enrichment analysis described above (Fig.…”

Section: Oral Gavage Of Responder Bacteria Reduces Tumor Size During mentioning

confidence: 99%

Predictable modulation of cancer treatment outcomes by the gut microbiota

et al. 2020

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The gut microbiota has the potential to influence the efficacy of cancer therapy. Here, we investigated the contribution of the intestinal microbiome on treatment outcomes in a heterogeneous cohort that included multiple cancer types to identify microbes with a global impact on immune response. Human gut metagenomic analysis revealed that responder patients had significantly higher microbial diversity and different microbiota compositions compared to non-responders. A machine-learning model was developed and validated in an independent cohort to predict treatment outcomes based on gut microbiota composition and functional repertoires of responders and non-responders. Specific species, Bacteroides ovatus and Bacteroides xylanisolvens, were positively correlated with treatment outcomes. Oral gavage of these responder bacteria significantly increased the efficacy of erlotinib and induced the expression of CXCL9 and IFN-γ in a murine lung cancer model. These data suggest a predictable impact of specific constituents of the microbiota on tumor growth and cancer treatment outcomes with implications for both prognosis and therapy.

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Section: Oral Gavage Of Responder Bacteria Reduces Tumor Size During mentioning

confidence: 99%

Predictable modulation of cancer treatment outcomes by the gut microbiota

et al. 2020

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“…Importantly, this internal timekeeper system is also involved in the absorption, distribution, metabolism, and elimination of drugs in vivo [14]. As a result, chronotherapy has been increasingly developed and employed in cancer and other disease therapies [15]. Many chemotherapy agents exhibit severe toxicity, such as bone marrow suppression, liver and kidney dysfunction, gastrointestinal reactions and decreased immune function.…”

Section: Discussionmentioning

confidence: 99%

Dosing‐time contributes to chronotoxicity of clofarabine in mice via means other than pharmacokinetics

Luan

Zhang

Liu

et al. 2016

The Kaohsiung J of Med Scie

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To evaluate the time- and dose-dependent toxicity of clofarabine in mice and to further define the chronotherapy strategy of it in leukemia, we compared the mortality rates, LD50s, biochemical parameters, histological changes and organ indexes of mice treated with clofarabine at various doses and time points. Plasma clofarabine levels and pharmacokinetic parameters were monitored continuously for up to 8 hours after the single intravenous administration of 20 mg/kg at 12:00 noon and 12:00 midnight by high performance liquid chromatography (HPLC)-UV method. Clofarabine toxicity in all groups fluctuated in accordance with circadian rhythms in vivo. The toxicity of clofarabine in mice in the rest phase was more severe than the active one, indicated by more severe liver damage, immunodepression, higher mortality rate, and lower LD50. No significant pharmacokinetic parameter changes were observed between the night and daytime treatment groups. These findings suggest the dosing-time dependent toxicity of clofarabine synchronizes with the circadian rhythm of mice, which might provide new therapeutic strategies in further clinical application.

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“…The goal of chronopharmacology is to increase the understanding of periodic and predictable changes in the effects and tolerance of drugs in tumor patients (in the field of tumor treatment) [168,169]. Several studies have described that anti-tumor effect of cancer drugs differs at the time of day of administration, and it might be a clinically important factor in cancer-treated patients that may prevent drug resistance [170].…”

Section: Chronopharmacology and Resistance To Targeted Therapiesmentioning

confidence: 99%

“…The impacts of timing on the anti-tumor effects of erlotinib have been investigated in the mouse model of Lewis lung cancer xenografts [170]. Results proposed that anti-tumor efficacy and toxicity of erlotinib on xenografts of NSCLC mice model is dependent on the time of day of administration.…”

Section: Chronopharmacology and Resistance To Targeted Therapiesmentioning

confidence: 99%

“…Results proposed that anti-tumor efficacy and toxicity of erlotinib on xenografts of NSCLC mice model is dependent on the time of day of administration. The effects may be associated with the EGFR-AKT/cyclin D1/cyclin-dependent kinase (CDK) 4 signaling pathway and might be a clinically important variable [170]. The association of chronopharmacology factors with cancer drug resistance has not been well studied, and more investigations are necessary to explore the effects for prevention of drug resistance.…”

Section: Chronopharmacology and Resistance To Targeted Therapiesmentioning

confidence: 99%

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Mechanisms of tumor cell resistance to the current targeted-therapy agents

et al. 2016

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Resistance to chemotherapy agents is a major challenge infront of cancer patient treatment and researchers. It is known that several factors, such as multidrug resistance proteins and ATP-binding cassette families, are cell membrane transporters that can efflux several substrates such as chemotherapy agents from the cell cytoplasm. To reduce the adverse effects of chemotherapy agents, various targeted-based cancer therapy (TBCT) agents have been developed. TBCT has revolutionized cancer treatment, and several agents have shown more specific effects on tumor cells than chemotherapies. Small molecule inhibitors and monoclonal antibodies are specific agents that mostly target tumor cells but have low side effects on normal cells. Although these agents have been very useful for cancer treatment, however, the presence of natural and acquired resistance has blunted the advantages of targeted therapies. Therefore, development of new options might be necessary. A better understanding of tumor cell resistance mechanisms to current treatment agents may provide an appropriate platform for developing and improving new treatment modalities. Therefore, in this review, different mechanisms of tumor cell resistance to chemotherapy drugs and current targeted therapies have been described.

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Chronopharmacology and Mechanism of Antitumor Effect of Erlotinib in Lewis Tumor-Bearing Mice

Cited by 9 publications

References 31 publications

Predictable modulation of cancer treatment outcomes by the gut microbiota

Predictable modulation of cancer treatment outcomes by the gut microbiota

Dosing‐time contributes to chronotoxicity of clofarabine in mice via means other than pharmacokinetics

Mechanisms of tumor cell resistance to the current targeted-therapy agents

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