Related Experiment Video

Updated: May 16, 2025

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.1K

Dual Targeting of Pim and PI3 Kinases in Mature T-Cell Lymphoma

M Lohrberg1, M Heber1, L Ries1

  • 1Haematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.

European Journal of Haematology
|April 1, 2025
PubMed

Insights

Targeting Provirus Integration site for Moloney leukemia virus (Pim) kinases shows promise for lymphoma treatment. Dual inhibition of Pim and PI3 kinases overcomes resistance, offering a new therapeutic strategy for mature T-cell lymphoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Provirus Integration site for Moloney leukemia virus (Pim) kinases are oncogenes frequently upregulated in mature T-cell lymphoma (mTCL).
  • Previous attempts to inhibit Pim kinases showed limited efficacy in mTCL cell viability.
  • Understanding resistance mechanisms is crucial for developing effective lymphoma therapies.

Purpose of the Study:

  • To investigate cellular responses to Pim kinase inhibition in mTCL.
  • To identify escape mechanisms that mitigate the anti-lymphoma effects of Pim inhibition.
  • To evaluate the therapeutic potential of dual Pim and PI3-kinase inhibition in mTCL.

Main Methods:

  • Analysis of cellular responses to Pim kinase inhibition.
  • Investigating PI3K/Akt/mTOR signaling pathway activation.
  • In vitro assessment of dual Pim/PI3K inhibitor (IBL-202) efficacy.
  • Evaluation of cell death induction and anti-apoptotic mechanisms.

Main Results:

  • PI3K/Akt-driven mTOR activation identified as a key escape mechanism against Pim inhibition.
  • Dual inhibition of Pim and PI3 kinases demonstrated synergistic anti-lymphoma effects in vitro.
  • IBL-202 induced potent cell-cycle-dependent cell death across various mTCL subtypes.
  • Downregulation of mTOR-induced protein translation and BCL-xL mitigation observed.

Conclusions:

  • Therapeutic inhibition of Pim kinases in mTCL is hampered by escape mechanisms involving PI3K/Akt/mTOR signaling.
  • Dual Pim and PI3-kinase inhibition represents a promising therapeutic strategy for mTCL.
  • The dual inhibitor IBL-202 shows significant potential for treating mature T-cell lymphoma.
Keywords:
AZD1208IBL‐202PI3KPim kinaseT‐cell lymphomalymphoma

More Related Videos

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells09:32

Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells

Published on: February 8, 2018

14.5K
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.1K

Related Concept Videos

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...
7.4K
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...
3.3K
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...
4.4K
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...
6.2K
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...
3.7K
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...
8.5K