Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

3.5K
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...
3.5K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

8.8K
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...
8.8K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

7.6K
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...
7.6K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

3.8K
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...
3.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

6.3K
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...
6.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

A human lysosomal storage disorder toolkit for decoding proteome landscapes in cortical-like and dopaminergic-like induced neurons.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

Discovery of Tcf7 regulators with clonally-resolved CRISPR screens identifies Trim28 as a mediator of CD8 T cell differentiation in tumors.

bioRxiv : the preprint server for biology·2026
Same author

Plasma proteomics improves thrombosis prediction in patients with cancer and identifies targetable IL-17-driven endothelial activation.

Science translational medicine·2026
Same author

Structural basis for regulation of the proteasome 20S core particle by the Parkinsonism-associated proteins FBXO7 and PI31.

bioRxiv : the preprint server for biology·2026
Same author

Publisher Correction: Tumor transcriptional state predicts survival in immune-checkpoint-blockade-treated glioblastoma.

Nature cancer·2026
Same author

Tumor transcriptional state predicts survival in immune-checkpoint-blockade-treated glioblastoma.

Nature cancer·2026
Same journal

Incoming US science academy chief vows to 'double down' on research.

Nature·2026
Same journal

Author Correction: Synthesis of enantioenriched atropisomers by biocatalytic deracemization.

Nature·2026
Same journal

Electrodeposited self-assembled molecules for perovskite photovoltaics.

Nature·2026
Same journal

Neutrino's nursery found: the 'Shadow Blaster'.

Nature·2026
Same journal

Dementia risk in middle-aged people linked to a blood protein.

Nature·2026
Same journal

Daily briefing: What's really happening with trust in science.

Nature·2026
See all related articles

Related Experiment Video

Updated: Jun 26, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.3K

Targetable leukaemia dependency on noncanonical PI3Kγ signalling.

Qingyu Luo1, Evangeline G Raulston1, Miguel A Prado2,3

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Nature
|May 8, 2024
PubMed
Summary
This summary is machine-generated.

This study reveals a new target for acute leukaemias: phosphoinositide-3-kinase-gamma (PI3Kγ) and its pathway. Inhibiting PI3Kγ shows promise in treating leukaemias, especially when combined with other therapies.

More Related Videos

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.1K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:39

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

77

Related Experiment Videos

Last Updated: Jun 26, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.3K
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.1K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:39

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

77

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Phosphoinositide-3-kinase-gamma (PI3Kγ) is known to affect anti-tumour immunity in solid cancers.
  • The specific roles of PI3Kγ within cancer cells, particularly in leukaemias, remain largely unknown.

Purpose of the Study:

  • To investigate the cell-intrinsic functions of PI3Kγ in acute leukaemias.
  • To identify potential therapeutic targets within PI3Kγ signaling pathways for leukaemia treatment.

Main Methods:

  • Genome-wide CRISPR interference screening was employed across various acute leukaemias.
  • Functional analyses were conducted to understand PI3Kγ pathway activation and downstream effects.
  • The study integrated genetic screening with biochemical and cellular assays.

Main Results:

  • A subset of acute leukaemias exhibits a dependency on the PI3Kγ complex, linked to PIK3R5 activation and innate inflammatory signaling.
  • PI3Kγ directly phosphorylates p21 (RAC1)-activated kinase 1 (PAK1), a key mediator of this dependency.
  • Inhibition of PI3Kγ impairs mitochondrial oxidative phosphorylation by affecting PAK1 dephosphorylation.
  • The PI3Kγ inhibitor eganelisib demonstrated efficacy in leukaemias with activated PIK3R5.
  • Combination therapy with eganelisib and cytarabine improved survival in preclinical models, even with low PIK3R5 expression.

Conclusions:

  • PI3Kγ-PAK1 signaling represents a targetable dependency in acute leukaemias.
  • Targeting PI3Kγ, particularly with eganelisib, offers a potential therapeutic strategy for leukaemias.
  • Combination therapies involving PI3Kγ inhibitors show enhanced efficacy and warrant clinical evaluation.