Related Experiment Video

Updated: Apr 30, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

1.1K

PI3K-dependent multiple myeloma cell survival is mediated by the PIK3CA isoform

Claudia Hofmann1, Thorsten Stühmer, Nadine Schmiedl

  • 1Division of Haematology and Oncology, Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.

British Journal of Haematology
|April 29, 2014
PubMed

Insights

Targeting PIK3CA, a specific form of phosphatidylinositide 3-kinase (PI3K), shows promise for treating multiple myeloma (MM). Inhibiting PIK3CA effectively kills MM cells and enhances existing therapies, suggesting its clinical potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Constitutive phosphatidylinositide 3-kinase (PI3K) signaling is crucial in multiple myeloma (MM) pathophysiology.
  • Targeting PI3K offers a potential therapeutic strategy for MM.
  • Isoform-specific inhibition may improve efficacy and reduce side effects.

Purpose of the Study:

  • To investigate the individual roles of PI3K isoforms (PIK3CA, PIK3CB, PIK3CD, PIK3CG) in MM cell survival and signaling.
  • To evaluate the efficacy of novel PI3K isoform-specific inhibitors in MM.

Main Methods:

  • Performed isoform-specific knockdown of PIK3CA, PIK3CB, PIK3CD, and PIK3CG.
  • Tested PI3K isoform-specific inhibitors: BYL-719 (PIK3CA), TGX-221 (PIK3CB), CAL-101 (PIK3CD), and CAY10505 (PIK3CG).
  • Assessed MM cell death and downstream signaling pathways.

Main Results:

  • PIK3CA is essential for constitutive Akt activity in MM cells.
  • PIK3CA blockade, unlike other isoform inhibitions, induced significant MM cell death in a subset of samples.
  • Combined treatment with PIK3CA inhibitor BYL-719 and standard anti-myeloma agents enhanced MM cell death.

Conclusions:

  • PIK3CA plays a critical role in MM cell survival.
  • PIK3CA inhibition demonstrates significant therapeutic potential in multiple myeloma.
  • PIK3CA inhibitors warrant further clinical evaluation for MM treatment.
Keywords:
cancerhaematologymultiple myelomaoncogenessignalling

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

951
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

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

Published on: July 21, 2018

19.0K

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...
5.1K
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...
3.6K
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...
10.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
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...
4.7K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K