Related Experiment Video

Updated: Jun 13, 2026

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
13:19

Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery

Published on: April 26, 2024

Dasatinib is preclinically active against Src-overexpressing human transitional cell carcinoma of the urothelium with

Jonathan M Levitt1, Hideyuki Yamashita, Weiguo Jian

  • 1Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.

Molecular Cancer Therapeutics
|April 22, 2010
PubMed

Insights

Dasatinib shows preclinical promise against Src-overexpressing transitional cell carcinoma (TCC). Combining dasatinib with cisplatin demonstrated significant antitumor activity in vivo, warranting further clinical investigation.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Transitional cell carcinoma (TCC) is a significant malignancy.
  • Src signaling pathway dysregulation is implicated in TCC progression.
  • Targeted therapies are being explored for TCC treatment.

Purpose of the Study:

  • To evaluate the preclinical efficacy of dasatinib, a multitargeted kinase inhibitor, against human TCC.
  • To assess the combination therapy of dasatinib and cisplatin in TCC models.
  • To investigate the role of Src expression in TCC response to dasatinib.

Main Methods:

  • Immunohistochemistry to assess Src expression in TCC tissue microarrays.
  • In vitro evaluation of dasatinib and cisplatin activity in human TCC cell lines.
  • Western blot analysis for Src and phosphorylated-Src (p-Src) expression.
  • In vivo assessment of dasatinib and combination therapy in murine xenograft models.

Main Results:

  • Src expression was observed in 62-75% of human TCC samples.
  • Dasatinib exhibited significant antiproliferative activity against cisplatin-resistant TCC cell lines with high Src and p-Src expression.
  • Combination therapy of dasatinib and cisplatin demonstrated enhanced antitumor activity, including proliferation inhibition and apoptosis induction in vivo.
  • Dasatinib effectively downregulated p-Src in both sensitive and resistant TCC cells.

Conclusions:

  • Dasatinib demonstrates preclinical antitumor activity in Src-overexpressing TCC with active Src signaling.
  • The combination of dasatinib and cisplatin shows significant synergistic efficacy in preclinical TCC models.
  • These findings support further clinical investigation of dasatinib, particularly in combination with cisplatin, for TCC patients with specific molecular profiles.

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...
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...
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...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...