Related Experiment Video

Updated: Apr 16, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

8.4K

The phosphoinositide 3-kinase pathway and therapy resistance in cancer

Kristin K Brown1, Alex Toker1

  • 1Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School 330 Brookline Avenue, EC/CLS 633A, Boston, MA 02215 USA.

F1000Prime Reports
|March 10, 2015
PubMed

Insights

The phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway drives cancer growth and therapy resistance. This review explores PI3K-driven resistance mechanisms and combination strategies to overcome them, enhancing anti-cancer treatment efficacy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway is crucial for cancer development and progression.
  • This signaling network is implicated in resistance to various anti-cancer treatments.
  • Understanding PI3K pathway's role in therapy resistance is vital for improving cancer treatment outcomes.

Purpose of the Study:

  • To review the mechanisms by which the PI3K pathway contributes to cancer therapy resistance.
  • To highlight potential combination therapy strategies that can overcome PI3K-driven resistance.
  • To discuss resistance mechanisms limiting the effectiveness of PI3K pathway inhibitors.

Main Methods:

  • Literature review of PI3K/Akt/mTOR signaling in cancer therapy resistance.
  • Analysis of preclinical and clinical studies on PI3K pathway inhibitors.
  • Synthesis of information on combination therapies targeting the PI3K pathway.

Main Results:

  • The PI3K pathway promotes resistance through various mechanisms, including altered signaling and activation of bypass pathways.
  • Combination strategies involving PI3K inhibitors with other anti-cancer agents show promise in preclinical models.
  • Intrinsic and acquired resistance mechanisms limit the efficacy of current PI3K inhibitors.

Conclusions:

  • The PI3K pathway is a significant driver of resistance to cancer therapies.
  • Targeting the PI3K pathway in combination with other treatments may overcome resistance and improve patient outcomes.
  • Further research is needed to fully elucidate resistance mechanisms and optimize combination therapy strategies.

More Related Videos

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

9.1K
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.4K

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...
6.5K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
8.0K
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...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.8K
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
11.3K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K