Related Experiment Video

Updated: Apr 21, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

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

Published on: January 22, 2019

9.7K

PIM kinases as potential therapeutic targets in a subset of peripheral T cell lymphoma cases

Esperanza Martín-Sánchez1, Lina Odqvist2, Socorro M Rodríguez-Pinilla3

  • 1Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Cancer Genomics Group, Marqués de Valdecilla Research Institute (IDIVAL) & Pathology Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain.

Plos One
|November 12, 2014
PubMed

Insights

Pan-PIM kinase inhibition effectively targets peripheral T cell lymphoma (PTCL) by inducing apoptosis. Combining PIM kinase inhibitors with ALK inhibitors shows promise for treating ALK-positive anaplastic large cell lymphoma (ALK+ ALCL).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Peripheral T cell lymphoma (PTCL) lacks effective therapies.
  • Proviral Integration site of Moloney murine leukemia virus (PIM) kinases are crucial for cell survival and are overexpressed in PTCL.

Purpose of the Study:

  • To evaluate the therapeutic potential of PIM kinase inhibition in PTCL.
  • To investigate PIM kinase overexpression in PTCL patients and cell lines.

Main Methods:

  • Genetic inhibition using small interfering and short hairpin RNAs.
  • Pharmacological inhibition using the pan-PIM inhibitor ETP-39010.
  • Assessed effects on cell viability, apoptosis, cell cycle, and gene expression in PTCL cell lines and primary T cells.

Main Results:

  • Individual PIM gene inhibition showed no effect due to compensatory mechanisms.
  • Pan-PIM inhibition strongly induced apoptosis in all PTCL cell lines, partly via DNA damage induction.
  • Pan-PIM inhibition synergized with Cisplatin and reduced tumoral T cell viability ex vivo without affecting normal T cells.
  • Simultaneous inhibition of ALK and PIM kinases demonstrated a strong synergistic effect in ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) cell lines.

Conclusions:

  • Pharmacological pan-PIM kinase inhibition is a potential therapeutic strategy for a subset of PTCL.
  • Combination therapy with PIM kinase inhibitors and ALK inhibitors shows significant promise for ALK+ ALCL treatment.

More Related Videos

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.8K
Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer07:55

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer

Published on: January 17, 2025

2.1K

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
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...
5.2K
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...
14.3K
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...
9.2K
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...
6.3K