Related Experiment Video

Updated: Feb 6, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 23, 2019

7.8K

Combined Inhibition of PI3Kβ and mTOR Inhibits Growth of PTEN-null Tumors

James T Lynch1, Urszula M Polanska1, Ursula Hancox2

  • 1Bioscience, Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.

Molecular Cancer Therapeutics
|August 12, 2018
PubMed

Insights

Combining PI3Kβ inhibitor AZD8186 with mTOR inhibitor vistusertib effectively suppresses PTEN-null tumors. This combination shows promise for treating various cancers by enhancing PI3K pathway inhibition.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Loss of PTEN tumor suppressor gene creates a dependency on PI3Kβ.
  • Sustained PI3K pathway inhibition is crucial for maximal tumor growth inhibition.
  • Tumor growth is often limited by incomplete PI3K inhibition or pathway reactivation.

Purpose of the Study:

  • To identify effective combination therapies for PTEN-null tumors.
  • To evaluate the synergistic effects of PI3Kβ inhibition with other kinase inhibitors.
  • To assess the antiproliferative and in vivo efficacy of AZD8186 combined with mTOR inhibitors.

Main Methods:

  • Extended cell proliferation assays were used to test drug combinations.
  • PTEN-null tumor cell lines and xenograft models were utilized.
  • Biomarker analysis (in vitro and in vivo) assessed pathway suppression and cellular changes.

Main Results:

  • Combination of PI3Kβ inhibitor AZD8186 and mTOR inhibitor vistusertib demonstrated the most potent antiproliferative effects.
  • The combination effectively controlled tumor growth in PTEN-null models of TNBC, prostate, and renal cancers.
  • Enhanced suppression of pNDRG1, p4EBP1, and HMGCS1, increased FOXO3 nuclear translocation, and reduced glucose uptake were observed.

Conclusions:

  • Combining AZD8186 and vistusertib offers a promising therapeutic strategy for PTEN-null tumors.
  • This combination achieves comprehensive PI3K signaling suppression.
  • Further investigation into this combination for PTEN-null cancer treatment is warranted.

More Related Videos

Deferred Growth Inhibition Assay to Quantify the Effect of Bacteria-derived Antimicrobials on Competition07:42

Deferred Growth Inhibition Assay to Quantify the Effect of Bacteria-derived Antimicrobials on Competition

Published on: September 3, 2016

15.5K
Pattern-Triggered Oxidative Burst and Seedling Growth Inhibition Assays in Arabidopsis thaliana04:11

Pattern-Triggered Oxidative Burst and Seedling Growth Inhibition Assays in Arabidopsis thaliana

Published on: May 21, 2019

14.0K

Related Concept Videos

Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.2K
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
92.6K
Inhibition of Cdk Activity02:34

Inhibition 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...
6.0K
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...
4.8K
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...
5.6K
Primary and Secondary Growth in Roots and Shoots03:02

Primary and Secondary Growth in Roots and Shoots

Vascular plants, which account for over 90% of the Earth’s vegetation, all undergo primary growth—which lengthens roots and shoots. Many land plants, notably woody plants, also undergo secondary growth—which thickens roots and shoots.
60.6K