Prognostic relevance of the mTOR pathway in renal cell carcinoma: implications for molecular patient selection for

Allan J Pantuck1, David B Seligson, Tobias Klatte

  • 1Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.

Cancer
|April 19, 2007
PubMed
Abstract

Insights

Targeting the mammalian target of rapamycin (mTOR) pathway in renal cell carcinoma (RCC) shows promise. Biomarkers like PTEN and pAkt can predict prognosis and patient selection for mTOR-targeted therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The mammalian target of rapamycin (mTOR) pathway is frequently dysregulated in human cancers.
  • Targeting the mTOR pathway is a promising therapeutic strategy currently under clinical investigation.
  • Renal cell carcinoma (RCC) represents a significant area for evaluating mTOR pathway inhibitors.

Purpose of the Study:

  • To investigate the role and potential of targeting the mTOR pathway in renal cell carcinoma (RCC).
  • To identify biomarkers within the mTOR pathway associated with RCC pathology and patient survival.
  • To assess the limitations and potential of mTOR-targeted therapies in RCC.

Main Methods:

  • Immunohistochemical analysis of pAkt, PTEN, p27, and pS6 expression in 375 RCC patient specimens.
  • Tissue microarray construction from paraffin-embedded tumor samples.
  • Correlation of protein expression with pathological parameters and patient survival data.

Main Results:

  • mTOR pathway alterations were more pronounced in clear-cell RCC, high-grade tumors, and those with poor prognostic features.
  • PTEN and pS6 expression strongly correlated with pathological parameters.
  • Specific expression levels of cytoplasmic pAkt, nuclear pAkt, PTEN, p27, and pS6 served as significant prognostic indicators for patient survival.
  • High nuclear pAkt expression indicated a favorable prognosis, while high cytoplasmic pAkt indicated a poor prognosis.

Conclusions:

  • mTOR pathway components are significantly linked to RCC pathological characteristics and survival outcomes.
  • The efficacy of mTOR-targeted therapy may vary across different RCC subtypes.
  • PTEN, pAkt, p27, and pS6 can function as biomarkers for patient selection and prognosis prediction in RCC.
  • Patients with highly activated mTOR pathways are likely to benefit most from targeted interventions.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...