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Updated: Feb 6, 2026

Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
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Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice

Published on: October 5, 2017

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TP53-dependence on the effect of doxorubicin and Src inhibitor combination therapy

Yun Sun Lee1, Ji-Yoon Choi1, Jeeyun Lee2

  • 11 Department of Orthopaedic Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|August 21, 2018
PubMed

Insights

Genetic alterations in the TP53 gene influence the effectiveness of combining doxorubicin with Src kinase inhibitors. This combination shows synergy in TP53-altered cancers but antagonism in wild-type TP53 cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • The therapeutic efficacy of Src kinase inhibitors in cancer treatment remains debated.
  • The TP53 gene status is a crucial factor in cancer progression and treatment response.

Purpose of the Study:

  • To investigate the association between TP53 gene alterations and the synergistic effects of combining doxorubicin with Src kinase inhibitors.
  • To determine the role of TP53 in mediating the response to this drug combination.

Main Methods:

  • Utilized human osteosarcoma (MG63, U2OS) and colon cancer cell lines.
  • Performed drug combination studies with doxorubicin and an Src kinase inhibitor.
  • Analyzed TP53 gene status and its impact on drug synergy using patient-derived cells.

Main Results:

  • Found a significant association between TP53 alterations and synergistic effects of doxorubicin plus Src kinase inhibitor.
  • Doxorubicin activates signal transducer and activator of transcription 3 (STAT3) via Src kinase in TP53-altered cells.
  • Src kinase inhibitor synergized with doxorubicin in TP53-altered cells but antagonized effects in wild-type TP53 cells.

Conclusions:

  • TP53 genetic alterations are critical determinants for the efficacy of combined doxorubicin and Src inhibitor therapy.
  • This finding has implications for personalized cancer treatment strategies based on TP53 mutational status.
Keywords:
Src kinaseTP53doxorubicindrug resistantsaracatinib (AZD0530)

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