Related Experiment Video

Updated: Apr 28, 2026

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

661

Sorafenib/regorafenib and lapatinib interact to kill CNS tumor cells

Hossein A Hamed1, Seyedmehrad Tavallai, Steven Grant

  • 1Molecular Biology, Virginia Commonwealth University, 401 College St., Richmond, VA, 23298.

Journal of Cellular Physiology
|June 10, 2014
PubMed

Insights

Sorafenib and lapatinib combination therapy demonstrates synergistic efficacy in killing central nervous system (CNS) tumor cells, offering a potential new glioblastoma treatment. This drug combination also enhances radiation toxicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Central nervous system (CNS) tumors, including glioblastoma, present significant therapeutic challenges.
  • Targeted therapies like multi-kinase inhibitors (sorafenib, regorafenib) and ERBB1/ERBB2 inhibitors (lapatinib) are crucial in cancer treatment.
  • Understanding drug interactions is vital for developing effective combination therapies.

Purpose of the Study:

  • To investigate the synergistic interaction between sorafenib (or regorafenib) and lapatinib against CNS tumor cells.
  • To explore the underlying molecular mechanisms of this drug combination's efficacy.
  • To evaluate the potential of this combination therapy, including its interaction with radiation, for glioblastoma treatment.

Main Methods:

  • Utilized multiple CNS tumor cell lines for in vitro drug sensitivity testing.
  • Assessed drug interactions using assays for cell death, apoptosis, and autophagy markers (LC3-GFP, LC3II, p62, LAMP2).
  • Employed gene knockdown (Beclin1, ATG5, FADD, CD95) and expression studies (c-FLIP-s, BCL-XL, dominant negative caspase 9, activated AKT, MEK1, mTOR) to elucidate mechanisms.
  • Investigated the combination's effect on radiation toxicity.

Main Results:

  • Sorafenib and lapatinib exhibited a greater than additive effect in inducing CNS tumor cell death, a finding replicated with regorafenib.
  • The drug combination enhanced radiation toxicity in brain cancer cells.
  • Mechanistic studies revealed modulation of autophagy (LC3-GFP vesicles, LC3II, p62, LAMP2 degradation) and apoptosis pathways (involving c-FLIP-s, BCL-XL, caspase 9, FADD, CD95).
  • Signaling pathways including AKT, MEK1, and mTOR were implicated in mediating resistance to the drug combination.

Conclusions:

  • The combination of sorafenib and lapatinib demonstrates significant synergistic anti-tumor activity against CNS tumor cells.
  • This drug combination impacts key cellular processes like autophagy and apoptosis, and its efficacy is modulated by specific signaling pathways.
  • Given that both drugs are FDA-approved, further clinical investigation into sorafenib and lapatinib as a glioblastoma therapy is warranted.

More Related Videos

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

8.5K
A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

2.3K

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...
7.0K
Treatment Resistant Cancers02:56

Treatment Resistant 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...
2.6K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K
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...
4.8K
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
8.2K
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...
3.6K