The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinoma

Zhou, Ledu; Huang, Yun; Li, Jingdong; Wang, Zhiming

doi:10.1007/s12032-009-9201-4

Cited by 191 publications

(150 citation statements)

References 29 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…Sirolimus has been shown in vivo to block mTOR kinase binding activity, which is a key step in the PI3K/Akt/mTOR pathway that regulates cell growth and proliferation (20). Overactivation of this pathway is frequently observed in malignant cells and is associated with poor prognosis after a cancer diagnosis (21)(22)(23). As such, a number of cancer treatments target the PI3K/Akt/mTOR pathway (24).…”

Section: Discussionmentioning

confidence: 99%

Sirolimus Use and Cancer Incidence Among US Kidney Transplant Recipients

Yanik

Gustafson

Kasiske

et al. 2015

American Journal of Transplantation

View full text Add to dashboard Cite

y Both authors contributed equally.Sirolimus has anti-carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population-based cancer registries and national pharmacy claims. Recipients contributed sirolimusexposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32 604 kidney transplants (5687 sirolimusexposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] ¼ 0.88, 95% confidence interval [CI] ¼ 0.70-1.11). Prostate cancer incidence was higher during sirolimus use (HR ¼ 1.86, 95% CI ¼ 1.15-3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR ¼ 0.74, 95% CI ¼ 0.57-0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection.Abbreviations: HR, hazard ratio; mTOR, mammalian target of rapamycin; PSA, prostate-specific antigen; SRTR, Scientific Registry for Transplant Recipients

show abstract

Section: Discussionmentioning

confidence: 99%

Sirolimus Use and Cancer Incidence Among US Kidney Transplant Recipients

Yanik

Gustafson

Kasiske

et al. 2015

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…104 Moreover, when it is overexpressed, it is associated with poor prognosis, invasion, and metastasis. 105 Despite this, a very low rate of genetic alterations that affect the mTOR pathway in HCC has been reported. 104 Recently, mTOR was identified as a direct target of miR-199a-3p, and to be inversely correlated with miR-199a-3p in HCC.…”

Section: 3mentioning

confidence: 99%

MicroRNAs in liver cancer: a model for investigating pathogenesis and novel therapeutic approaches

et al. 2014

View full text Add to dashboard Cite

MicroRNAs (miRNAs) constitute a large class of short RNAs (e.g., 20-24 nucleotides in length), whose main function is to posttranscriptionally regulate the expression of protein-coding genes. Their importance in tumorigenesis has been demonstrated over the past decade, and correspondingly, they have emerged as potential therapeutic molecules and targets. Liver cancer is one of the most common neoplastic diseases worldwide, and it currently has a poor prognosis owing to largely ineffective therapeutic options. Liver cancer is also an excellent model for testing miRNA-based therapy approaches as it can be easily targeted with the systemic delivery of oligonucleotides. In recent years, the role of miRNAs in hepatocellular carcinoma (HCC) has been established with molecular studies and the development of animal models. These studies have also provided the basis for evaluating the therapeutic potential of miRNAs, or anti-miRNAs. In general, the safety of miRNAs has been proven and antitumor activity has been observed. Moreover, because of the absence or presence of mild side effects, the prophylactic use of miRNA-based approaches may be foreseen.

show abstract

“…42 Activation of this pathway is a common feature of a wide range of human cancers 43 and is an indicator of poor prognosis. [44][45][46][47][48] Thus, it is reasonable to assume that targeting mTOR using the orally active rapamycin derivative RAD001 can effectively contribute to treat tumors with hyperactivation of PI3K/ Akt/mTOR signaling. In this study, we demonstrated the efficacy of RAD001 as a potential therapeutic inhibitor of the PI3K/Akt/mTOR pathway in B-pre ALL cells.…”

Section: Dual Mtor/akt Inhibition In B-pre All Lm Neri Et Almentioning

confidence: 99%

Targeting the PI3K/Akt/mTOR signaling pathway in B-precursor acute lymphoblastic leukemia and its therapeutic potential

et al. 2013

View full text Add to dashboard Cite

B-precursor acute lymphoblastic leukemia (B-pre ALL) is a malignant disorder characterized by the abnormal proliferation of B-cell progenitors. The prognosis of B-pre ALL has improved in pediatric patients, but the outcome is much less successful in adults. Constitutive activation of the phosphatidylinositol 3-kinase (PI3K), Akt and the mammalian target of rapamycin (mTOR) (PI3K/Akt/ mTOR) network is a feature of B-pre ALL, where it strongly influences cell growth and survival. RAD001, a selective mTORC1 inhibitor, has been shown to be cytotoxic against many types of cancer including hematological malignancies. To investigate whether mTORC1 could represent a target in the therapy of B-pre ALL, we treated cell lines and adult patient primary cells with RAD001. We documented that RAD001 decreased cell viability, induced cell cycle arrest in G 0 /G 1 phase and caused apoptosis in B-pre ALL cell lines. Autophagy was also induced, which was important for the RAD001 cytotoxic effect, as downregulation of Beclin-1 reduced drug cytotoxicity. RAD001 strongly synergized with the novel allosteric Akt inhibitor MK-2206 in both cell lines and patient samples. Similar results were obtained with the combination CCI-779 plus GSK 690693. These findings point out that mTORC1 inhibitors, either as a single agent or in combination with Akt inhibitors, could represent a potential therapeutic innovative strategy in B-pre ALL.

show abstract

The mTOR pathway is associated with the poor prognosis of human hepatocellular carcinoma

Abstract: Expression of the mTOR pathway components, which are related with the transferability and invasive capacity of HCC cells, may be used as prognostic indicators in HCC.

Cited by 191 publications

References 29 publications

Sirolimus Use and Cancer Incidence Among US Kidney Transplant Recipients

Sirolimus Use and Cancer Incidence Among US Kidney Transplant Recipients

MicroRNAs in liver cancer: a model for investigating pathogenesis and novel therapeutic approaches

Targeting the PI3K/Akt/mTOR signaling pathway in B-precursor acute lymphoblastic leukemia and its therapeutic potential

Contact Info

Product

Resources

About