Combination of metformin with chemotherapeutic drugs via different molecular mechanisms

Peng, Mei; Darko, Kwame Oteng; Tao, Ting; Huang, Yanjun; Su, Qiongli; He, Caimei; Yin, Tao; Liu, Zhao‐Qian; Yang, Xiao‐Ping

doi:10.1016/j.ctrv.2017.01.005

Cited by 91 publications

(70 citation statements)

References 92 publications

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“…The clinical data showed that metformin‐treated patients have reduced PD‐L1 levels with increased phospho‐AMPK, confirming the bench findings . In this minireview, we updated the combination of metformin with clinically used targeted drugs including small molecule inhibitors and Abs, summed up in Figure . Most studies drawing on both in vitro and in vivo data have shown promising synergy of metformin with these targeted drugs.…”

Section: Discussionmentioning

confidence: 54%

“…Activation of AMPK and inhibition of mitochondria complex I are two major mechanisms of action . It showed significant synergy with chemotherapeutic drugs in both in vitro and in vivo models through broad‐spectrum action mechanisms, as we previously described . More interestingly, both preclinical and clinical evidence has profoundly indicated the improvement of targeted therapeutic efficacies by combining metformin with targeted drugs, including our recent report .…”

Section: Introductionmentioning

confidence: 57%

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Novel application of metformin combined with targeted drugs on anticancer treatment

et al. 2018

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The success of targeted drug therapies for treating cancer patients has attracted broad attention both in the academic community and social society. However, rapidly developed acquired resistance is becoming a newly recognized major challenge to the continuing efficiency of these therapies. Metformin is a well‐known natural compound with low toxicity derived from the plant French lilac. Our previous work has highlighted research progress of the combination of clinically applied chemotherapies and metformin by different mechanisms. We have also launched a study to combine metformin with the small molecule targeted drug gefitinib to treat bladder cancer using intravesical administration. Thus, in this minireview, we summarize recent achievements combining metformin with various targeted therapies. This work directs the potential clinical future by selecting available cancer patients and providing precise medicine by the combination of metformin and targeted drugs to overcome resistance and enhance therapeutic efficacies.

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Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 57%

Novel application of metformin combined with targeted drugs on anticancer treatment

et al. 2018

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“…It can also be applied with drugs involved in cellular metabolism or in the synthesis, where effectiveness is improved with new strategies such as immunotherapy [25]. Recently, the use of metformin has been combined with tyrosine kinase inhibitors (imatinib, sorafenib), and it has been effective in improving responses in cases of not only chronic myeloid leukemia but also myeloid leukemia with mutations in FLT3/ITD [28, 29]. Regarding the association between high ABCB1 gene expression and the activation of energy-dependent P (gp170) glycoprotein (ATP), energy depletion is an attractive strategy to overcome resistance to different drugs, including cytotoxic drugs (daunorubicin, doxorubicin, etoposide, vincristine or vinblastine, and mitoxantrone) or even antibiotics [10, 31–34].…”

Section: Discussionmentioning

confidence: 99%

Effect of metformin on the survival of patients with ALL who express high levels of the ABCB1 drug resistance gene

et al. 2018

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BackgroundIn acute lymphoblastic leukemia (ALL), high ABCB1 gene expression has been associated with treatment resistance, which affects patient prognosis. Many preclinical reports and retrospective population studies have shown an anti-cancer effect of metformin. Therefore, the objective of this study was to assess the effect of metformin on the treatment regimen in patients with ALL who exhibited high levels of ABCB1 gene expression and to determine its impact on overall survival.MethodsA total of 102 patients with ALL were recruited; one group (n = 26) received metformin, and the other received chemotherapy (n = 76). Measurement of ABCB1 transcript expression was performed using qRT-PCR prior to treatment initiation. Survival analysis was performed using Kaplan–Meier curves. The impact of both the type of treatment and the level of expression on the response (remission or relapse) was analyzed by calculating the odds ratio.ResultsThe survival of patients with high ABCB1 expression was lower than those with low or absent ABCB1 gene expression (p = 0.030). In the individual analysis, we identified a benefit to adding metformin in the group of patients with high ABCB1 gene expression (p = 0.025). In the metformin user group, the drug acted as a protective factor against both therapeutic failure (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.0037–1.53) and early relapse (OR 0.05, 95% CI 0.0028–1.153).ConclusionThe combined use of metformin with chemotherapy is effective in patients with elevated levels of ABCB1 gene expression. Trial registration NCT 03118128: NCT

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“…It has recently been identified that metformin has an anticancer effect and is used in combination with chemotherapeutic agents to reduce the dose of chemodrug and increase the efficacy. Metformin works on endometrial cancer through inhibition of cell proliferation and modulation of the mTOR pathway (18) and increases response to treatment (19). Metformin acts through increasing the expression of PgR gene (20), reducing the expression of glyoxalase I (21), regulating rapamycine pathway, an additive effect on AMPK phosphorylation in the ECC-1 cell line, and blocking epidermal growth factor signaling pathway in order to inhibit cellular proliferation and improve progestin treatment (22).…”

Section: Discussionmentioning

confidence: 99%

The Comparative Effect of Combination of Metformin and Megestrol Acetate With Megestrol Acetate Alone on Endometrial Growth Disorders

Sayyah-Melli¹,

Pourazad²,

Gharebaghi³

et al. 2017

International Journal of Women’s Health and Reproduction Scienc

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Combination of metformin with chemotherapeutic drugs via different molecular mechanisms

Cited by 91 publications

References 92 publications

Novel application of metformin combined with targeted drugs on anticancer treatment

Novel application of metformin combined with targeted drugs on anticancer treatment

Effect of metformin on the survival of patients with ALL who express high levels of the ABCB1 drug resistance gene

The Comparative Effect of Combination of Metformin and Megestrol Acetate With Megestrol Acetate Alone on Endometrial Growth Disorders

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