Related Experiment Video

Updated: Oct 3, 2026

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
08:38

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Published on: November 7, 2015

17.4K

Temsirolimus inhibits cell growth in combination with inhibitors of the B-cell receptor pathway

Anna-Katharina Zoellner1,2, Stephan Bayerl2, Grit Hutter2

  • 1a Department of Internal Medicine III , University Hospital Munich-Großhadern , Germany.

Leukemia & Lymphoma
|August 4, 2015
PubMed

Insights

Temsirolimus effectively reduced lymphoma cell growth. Combining it with PI3K-δ or BTK inhibitors showed additive effects, but bortezomib revealed antagonism, possibly due to increased pro-survival kinases.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • mTOR inhibitors are clinically relevant for malignant lymphoma.
  • Rapamycin derivatives can activate pro-survival feedback loops via PI3K-Akt.
  • Understanding drug interactions is crucial for optimizing lymphoma treatment.

Purpose of the Study:

  • To evaluate the efficacy of temsirolimus, a mTOR inhibitor, in diffuse large B-cell lymphoma (DLBCL) subtypes.
  • To investigate the additive or antagonistic effects of combining temsirolimus with other targeted therapies (PI3K-δ inhibitor, BTK inhibitor, bortezomib).
  • To explore the underlying molecular mechanisms of drug interactions.

Main Methods:

  • Cell growth assays were performed on GCB and ABC DLBCL cell lines.
  • Combination treatments included temsirolimus with idelalisib (PI3K-δ inhibitor), ibrutinib (BTK inhibitor), or bortezomib.
  • Western blot analysis was used to assess the levels of phosphorylated Akt and PDK.

Main Results:

  • Temsirolimus reduced cell growth in both GCB (30-66%) and ABC (45-57%) DLBCL.
  • Combination with idelalisib or ibrutinib showed additive effects on lymphoma cell growth.
  • Bortezomib demonstrated an antagonistic effect with temsirolimus in some GCB lymphoma, associated with increased p-Akt and p-PDK.

Conclusions:

  • Temsirolimus is effective against DLBCL, with additive benefits when combined with PI3K-δ or BTK inhibitors.
  • The combination of temsirolimus and bortezomib may be antagonistic in certain lymphoma subtypes.
  • Upregulation of pro-survival kinases (Akt, PDK) may mediate resistance to combination therapy.
Keywords:
DLBCLPI3KmTORtemsirolimus

More Related Videos

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 21, 2019

9.5K
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice07:02

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice

Published on: August 22, 2019

7.7K

Related Concept Videos

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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
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 specific...
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 rapamycin-insensitive companion...
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...