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Related Concept Videos

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...
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...
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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

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Related Experiment Video

Updated: Jun 4, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

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Targeting the PI3K/Akt/mTOR pathway--beyond rapalogs.

Ben Markman1, Rodrigo Dienstmann2, Josep Tabernero2

  • 1Centre for Cancer Research, Monash Institute of Medical Research, Southern Health, Melbourne, Victoria, Australia.

Oncotarget
|February 15, 2011
PubMed
Summary

The PI3K pathway is crucial in cancer development. New drug inhibitors targeting PI3K, Akt, and mTOR are in clinical trials, aiming to improve cancer treatment outcomes beyond current therapies.

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Last Updated: Jun 4, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
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Published on: July 21, 2018

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma
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Published on: March 3, 2023

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The phosphoinositide 3-kinase (PI3K) pathway is integral to cellular functions implicated in cancer progression.
  • Targeting this pathway therapeutically is a key strategy in cancer drug development.
  • While upstream inhibitors show success, downstream agents like rapalogs have had limited clinical impact.

Purpose of the Study:

  • To review the role of the PI3K pathway in cancer.
  • To discuss the clinical efficacy and limitations of current therapeutic strategies targeting this pathway.
  • To highlight the potential of novel PI3K, Akt, and mTOR inhibitors in cancer treatment.

Main Methods:

  • Literature review of PI3K pathway signaling in cancer.
  • Analysis of clinical trial data for PI3K pathway inhibitors.
  • Discussion of emerging therapeutic agents targeting downstream components.

Main Results:

  • Receptor tyrosine kinase inhibitors targeting upstream nodes have shown clinical success.
  • Rapalogs, targeting downstream effectors, have yielded disappointing clinical results in many tumor types.
  • Novel inhibitors of PI3K, Akt, and mTORC1/2 are progressing through early-phase clinical trials.

Conclusions:

  • The PI3K pathway remains a critical target for cancer therapy.
  • Newer agents targeting PI3K, Akt, and mTOR may overcome limitations of earlier downstream inhibitors.
  • These novel inhibitors hold promise for improved cancer patient outcomes.