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Prognostic markers in renal cell carcinoma: A focus on the 'mammalian target of rapamycin' pathway.

Youssef RF, Cost NG, Darwish OM, Margulis V - Arab J Urol (2012)

Bottom Line: Growing evidence suggests that mTOR deregulation is associated with many types of human cancer, including RCC.Consequently, temsirolimus and everolimus, which target mTOR, are approved for treating advanced RCC.Combining newly discovered molecular markers with classic clinicopathological prognostics might potentially improve the management of RCC.

View Article: PubMed Central - PubMed

Affiliation: Division of Urologic Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

ABSTRACT

Objectives: Increased knowledge about the molecular pathways involved in tumorigenesis has led to the discovery of new prognostic molecular markers and development of novel targeted therapies for renal cell carcinoma (RCC). In this review we describe the prognostic markers of RCC and highlight the areas of recent discovery with a focus on the mammalian target of rapamycin (mTOR) pathway.

Methods: We reviewed previous reports, using PubMed with the search terms 'renal cell carcinoma', 'molecular markers', 'prognosis', 'outcomes' and 'mammalian target of rapamycin pathway' published in the last two decades. We created a library of 100 references and focused on presenting the recent advances in the field.

Results: Growing evidence suggests that mTOR deregulation is associated with many types of human cancer, including RCC. Consequently, temsirolimus and everolimus, which target mTOR, are approved for treating advanced RCC. There is a demand to integrate clinical, pathological and molecular markers into accurate prognostic models to provide patients with the most personalised cancer care possible.

Conclusions: The mTOR pathway is highly implicated in RCC tumorigenesis and progression, and its constituents might represent a promising prognostic tool and target for treating RCC. Combining newly discovered molecular markers with classic clinicopathological prognostics might potentially improve the management of RCC.

No MeSH data available.


Related in: MedlinePlus

The mTOR pathway and its interactions with other important pathways and cellular process relevant to cancer.
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f0005: The mTOR pathway and its interactions with other important pathways and cellular process relevant to cancer.

Mentions: Fig. 1 illustrates the mTOR pathway and its relation to many cellular process and pathways. Growth factors like IGF, epidermal growth factor, platelet-derived growth factor and VEGF bind to and activate tyrosine kinase receptors (TKRs). Activated TKRs induce intracellular signalling cascades via PI3K/Akt, which in turn activates many cellular processes, including cell growth, proliferation, survival, angiogenesis and metabolism. TKRs also activate Ras, which not only activates the mitogen activated protein kinase pathway, but also activates PI3K, leading to the activation of mTOR [16]. Activated Akt inhibits tuberous sclerosis complex TSC1 and TSC2, the natural inhibitors of mTOR [17]. PTEN, a tumour-suppressor gene located on chromosome 10, antagonises PI3K function, negatively regulating Akt/mTOR activity and ultimately terminating the intracellular PI3K signalling cascade [18]. PTEN is absent or decreased in many cancers, and its deletion is associated with the metastatic disease in RCC [19]. Cells deficient in PTEN show high activity of the Akt/mTOR survival pathway, which makes them resistant to apoptosis, with a potential contribution to therapeutic resistance.


Prognostic markers in renal cell carcinoma: A focus on the 'mammalian target of rapamycin' pathway.

Youssef RF, Cost NG, Darwish OM, Margulis V - Arab J Urol (2012)

The mTOR pathway and its interactions with other important pathways and cellular process relevant to cancer.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4442886&req=5

f0005: The mTOR pathway and its interactions with other important pathways and cellular process relevant to cancer.
Mentions: Fig. 1 illustrates the mTOR pathway and its relation to many cellular process and pathways. Growth factors like IGF, epidermal growth factor, platelet-derived growth factor and VEGF bind to and activate tyrosine kinase receptors (TKRs). Activated TKRs induce intracellular signalling cascades via PI3K/Akt, which in turn activates many cellular processes, including cell growth, proliferation, survival, angiogenesis and metabolism. TKRs also activate Ras, which not only activates the mitogen activated protein kinase pathway, but also activates PI3K, leading to the activation of mTOR [16]. Activated Akt inhibits tuberous sclerosis complex TSC1 and TSC2, the natural inhibitors of mTOR [17]. PTEN, a tumour-suppressor gene located on chromosome 10, antagonises PI3K function, negatively regulating Akt/mTOR activity and ultimately terminating the intracellular PI3K signalling cascade [18]. PTEN is absent or decreased in many cancers, and its deletion is associated with the metastatic disease in RCC [19]. Cells deficient in PTEN show high activity of the Akt/mTOR survival pathway, which makes them resistant to apoptosis, with a potential contribution to therapeutic resistance.

Bottom Line: Growing evidence suggests that mTOR deregulation is associated with many types of human cancer, including RCC.Consequently, temsirolimus and everolimus, which target mTOR, are approved for treating advanced RCC.Combining newly discovered molecular markers with classic clinicopathological prognostics might potentially improve the management of RCC.

View Article: PubMed Central - PubMed

Affiliation: Division of Urologic Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

ABSTRACT

Objectives: Increased knowledge about the molecular pathways involved in tumorigenesis has led to the discovery of new prognostic molecular markers and development of novel targeted therapies for renal cell carcinoma (RCC). In this review we describe the prognostic markers of RCC and highlight the areas of recent discovery with a focus on the mammalian target of rapamycin (mTOR) pathway.

Methods: We reviewed previous reports, using PubMed with the search terms 'renal cell carcinoma', 'molecular markers', 'prognosis', 'outcomes' and 'mammalian target of rapamycin pathway' published in the last two decades. We created a library of 100 references and focused on presenting the recent advances in the field.

Results: Growing evidence suggests that mTOR deregulation is associated with many types of human cancer, including RCC. Consequently, temsirolimus and everolimus, which target mTOR, are approved for treating advanced RCC. There is a demand to integrate clinical, pathological and molecular markers into accurate prognostic models to provide patients with the most personalised cancer care possible.

Conclusions: The mTOR pathway is highly implicated in RCC tumorigenesis and progression, and its constituents might represent a promising prognostic tool and target for treating RCC. Combining newly discovered molecular markers with classic clinicopathological prognostics might potentially improve the management of RCC.

No MeSH data available.


Related in: MedlinePlus