Related Experiment Video
Updated: Jun 25, 2026
08:04
Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
[Topics in mTOR pathway and its inhibitors]
C Dreyer1, M-P Sablin, S Faivre
1Service inter-hospitalier de cancérologie, hôpital Beaujon, 100, boulevard du Général-Leclerc, 92118 Clichy Cedex.
Bulletin Du Cancer
|February 13, 2009
Summary
The PI3K/AKT/mTOR pathway is crucial in cancer. Inhibitors like rapamycin analogs show promise in treating cancers, particularly metastatic renal cancers, with ongoing research exploring new applications and predictive factors.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The Phosphatidylinositol 3-kinase/Protein Kinase B/Mammalian Target of Rapamycin (PI3K/AKT/mTOR) pathway is vital for cell growth, survival, and cell cycle regulation.
- Dysregulation of the PI3K/AKT/mTOR pathway is frequently observed in various human cancers, making it a significant therapeutic target.
- Rapamycin, an mTOR inhibitor initially used for immunosuppression, and its analogs (temsirolimus, everolimus, deforolimus) have emerged as potential anticancer agents.
Purpose of the Study:
- To review the role of the PI3K/AKT/mTOR pathway in cancer.
- To discuss the therapeutic potential of mTOR inhibitors, specifically rapamycin analogs, in preclinical and clinical settings.
- To highlight ongoing research into new indications, combination therapies, and predictive biomarkers for these targeted agents.
Main Methods:
- Literature review of preclinical studies on cancer cell lines.
- Analysis of clinical trial data for rapamycin analogs in various cancers.
- Examination of studies investigating AKT inhibitors and combination therapies.
Main Results:
- Rapamycin analogs like temsirolimus and everolimus have shown efficacy in metastatic renal cancers.
- Preclinical studies indicate promising results for these analogs in various cancer cell lines.
- An AKT inhibitor, perifosin, did not demonstrate significant activity in clinical studies.
- Ongoing research is exploring new indications for mTOR inhibitors, both as monotherapy and in combination with chemotherapy or other targeted therapies.
Conclusions:
- The PI3K/AKT/mTOR pathway represents a critical target for anticancer drug development.
- Rapamycin analogs demonstrate clinical efficacy in specific cancer types, warranting further investigation.
- Identifying predictive factors for treatment sensitivity is essential for optimizing the use of these targeted therapies.
Related Concept Videos
03:03mTOR 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...
The mTOR pathway or the...
03:03mTOR 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...
The mTOR pathway or the...
01:22PI3K/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...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:34Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
02:57Targeted 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...
There are several types of targeted therapies against specific...