Related Experiment Video

Updated: Jun 27, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

Ruxolitinib inhibits CaMKII-γ to reverse bortezomib resistance in multiple myeloma

Ruqi Liang1,2, Hong Liu1,3, Xushan Zhong1

  • 1College of Chemistry and Chemical Engineering, Taiyuan University of Technology, Taiyuan, China.

Communications Biology
|June 25, 2026
PubMed

Insights

Multiple myeloma drug resistance is a major challenge. Researchers found that inhibiting CaMKII-gamma using ruxolitinib can overcome bortezomib resistance by targeting the AMPK-ULK1-autophagy pathway.

Area of Science:

  • Hematologic Malignancies
  • Cancer Biology
  • Drug Discovery

Background:

  • Multiple myeloma (MM) is a prevalent hematologic malignancy with increasing incidence and earlier onset.
  • Therapeutic resistance to agents like bortezomib is a significant clinical challenge in MM management.
  • Understanding the molecular basis of bortezomib resistance is crucial for developing effective treatment strategies.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying bortezomib resistance in multiple myeloma.
  • To identify novel therapeutic targets and strategies to overcome drug resistance in MM.
  • To investigate the role of calcium/calmodulin-dependent protein kinase II gamma (CaMKII-γ) in bortezomib-resistant MM (BRMM).

Main Methods:

  • Utilized high-throughput screening to identify CaMKII-γ inhibitors.
  • Investigated the AMPK-ULK1-autophagy axis in relation to CaMKII-γ activity.
  • Evaluated the efficacy of ruxolitinib in vitro using bortezomib-resistant MM cell lines (U266, KMS11).
  • Assessed ruxolitinib's efficacy in vivo using a mouse model of bortezomib-resistant MM.

Main Results:

  • Identified CaMKII-γ as a key regulator of bortezomib resistance in MM through the AMPK-ULK1-autophagy pathway.
  • Discovered ruxolitinib as a selective inhibitor of CaMKII-γ with the ability to reverse BRMM.
  • Demonstrated that ruxolitinib exhibits comparable efficacy to genetic CaMKII-γ ablation in preclinical models.
  • Showcased ruxolitinib's effectiveness in both in vitro and in vivo models of bortezomib resistance.

Conclusions:

  • CaMKII-γ plays a critical role in mediating bortezomib resistance in multiple myeloma via the AMPK-ULK1-autophagy pathway.
  • Ruxolitinib, a CaMKII-γ inhibitor, shows significant potential as a therapeutic agent to overcome bortezomib resistance in MM.
  • Targeting CaMKII-γ with ruxolitinib offers a promising strategy to improve treatment outcomes for patients with resistant multiple myeloma.

More Related Videos

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

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...
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...
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...
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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...