Everolimus: A New Mammalian Target of Rapamycin Inhibitor for the Treatment of Advanced Renal Cell Carcinoma

Grgic, Tatjana; Mis, Lydia; Hammond, Julia M

doi:10.1345/aph.1m288

Cited by 20 publications

(10 citation statements)

References 15 publications

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“…It is possible that destruction to the kidney's tubules and interstitium stemming from RCC [26], may contribute to dysfunctional reabsorptive processes and concomitant hyperglycemia. In addition, while the role that the kidney plays in the excretion of everolimus is minor [27], the majority of RCC patients in our study had undergone nephrectomies [2], raising the possibility of impaired renal elimination of everolimus. The mechanisms underlying the unfavorable hyperglycemic outcomes seen in this study remain unclear and undoubtedly necessitate further study.…”

Section: Discussionmentioning

confidence: 84%

Risk of hyperglycemia attributable to everolimus in cancer patients: A meta-analysis

Shameem

2016

Acta Oncologica

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Section: Discussionmentioning

confidence: 84%

Risk of hyperglycemia attributable to everolimus in cancer patients: A meta-analysis

Shameem

2016

Acta Oncologica

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“…Inhibition of mTOR has been demonstrated to suppress liver tumor growth and metastasis (9,10). Several clinical and preclinical studies have demonstrated that the mTOR inhibitor rapamycin and its analogues can be used to treat various types of solid tumor, including esophageal squamous cell carcinoma (11), lung cancer (12), renal cell carcinoma (13) and prostate cancer (14). Therefore, the mTOR pathway may be a prospective target for the treatment of HCC.…”

Section: Introductionmentioning

confidence: 99%

Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel-7402/5-fluorouracil cells

Ling

Tian

Zhang

et al. 2014

Molecular Medicine Reports

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Metformin exhibits anti-proliferative effects in tumor cells in vitro and in vivo. The present study investigated the ability of metformin to reverse multidrug resistance (MDR) in human hepatocellular carcinoma Bel-7402/5-fluorouracil (5-Fu; Bel/Fu) cells. The synergistic anti-proliferative effect of metformin combined with 5-Fu was evaluated using a Cell Counting kit-8 assay. The variation in apoptotic rates and cell cycle distribution were evaluated using a flow cytometric assay and variations in target gene and protein expression were monitored using reverse transcription-polymerase chain reaction and western blot analysis. The results demonstrated that metformin had a synergistic anti-proliferative effect with 5-Fu in the Bel/Fu cells. The variations in the number of apoptotic cells and distribution of the cell cycle were consistent with the variability in cell viability. Metformin targeted the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, suppressed the expression of hypoxia-inducible factor-1α (HIF-1α) and transcriptionally downregulated the expression of multidrug resistance protein 1/P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1). Collectively, these findings suggested that metformin may target the AMPK/mTOR/HIF-1α/P-gp and MRP1 pathways to reverse MDR in hepatocellular carcinoma.

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“…6–8 To date, only 1 study has been published that examined the efficacy and safety of TT in patients with mRCC requiring HD. Masini and colleagues conducted a retrospective study of 24 patients with mRCC who were treated with sunitinib (16 patients) or sorafenib (8 patients).…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Patients With Metastatic Renal Cell Carcinoma and End-Stage Renal Disease Receiving Dialysis and Targeted Therapies: A Single Institution Experience

Shetty¹,

Matrana

Atkinson

et al. 2014

Clinical Genitourinary Cancer

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Data are limited regarding outcomes in patients with end-stage renal disease (ESRD) and metastatic renal cell carcinoma (mRCC) receiving targeted therapy. We retrospectively identified patients with mRCC and ESRD treated at the University of Texas M.D. Anderson Cancer Center from 2002 to 2012. Fourteen patients were identified with a median number of targeted therapies (TTs) per patient of 3 (range, 1–4). Outcomes in patients with mRCC and ESRD were similar to those reported in patients with normal kidney function. Introduction Limited data are available regarding patients with renal cell carcinoma and ESRD treated with TTs. The objective of this study was to explore the tolerability and safety of TT in patients with mRCC and ESRD. Patients and Methods We retrospectively identified patients with mRCC and ESRD treated at the University of Texas M.D. Anderson Cancer Center from 2002 to 2012. Patient characteristics including demographic, histology, treatment, and adverse events are reported. Duration of treatment (TOT) was determined from date of drug initiation to discontinuation. Overall survival (OS) was determined from initiation of TT to death. Statistics are descriptive. Results Fourteen patients were identified. Ten patients had clear-cell histology and 4 had papillary histology. The median number of TTs per patient was 3 (range, 1–4) with median TOT of 28 months for all TTs. Eighty-eight percent of all toxicities were Grade 1 to 2; no Grade 4 toxicities were noted. Treatment discontinuations included 3 patients treated with sorafenib due to hand-foot syndrome, intolerable fatigue, and squamous cell skin cancer development; 2 patients treated with pazopanib due to intolerable fatigue and increased transaminase levels; and 1 patient treated with everolimus due to pneumonitis. Eight patients died from progressive disease. Median OS from initiation of TT was 28.5 months and 35 months from time of diagnosis. Conclusion Toxicities were mild to moderate and consistent with those reported in previous studies. TTs appear to be safe, well tolerated and produce antitumor response in patients with mRCC and ESRD receiving dialysis.

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Everolimus: A New Mammalian Target of Rapamycin Inhibitor for the Treatment of Advanced Renal Cell Carcinoma

Abstract: Based on a review of the currently available literature, everolimus provides a safe and efficacious treatment option for patients with renal cell carcinoma who have progressed on treatment with sunitinib and/or sorafenib.

Cited by 20 publications

References 15 publications

Risk of hyperglycemia attributable to everolimus in cancer patients: A meta-analysis

Risk of hyperglycemia attributable to everolimus in cancer patients: A meta-analysis

Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel-7402/5-fluorouracil cells

Outcomes of Patients With Metastatic Renal Cell Carcinoma and End-Stage Renal Disease Receiving Dialysis and Targeted Therapies: A Single Institution Experience

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