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Related Concept Videos

Preclinical Development: Overview01:28

Preclinical Development: Overview

Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...

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Dose Uptake of Platinum- and Ruthenium-based Compound Exposure in Zebrafish by Inductively Coupled Plasma Mass Spectrometry with Broader Applications
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Initial testing of cisplatin by the pediatric preclinical testing program.

Mimi Tajbakhsh1, Peter J Houghton, Christopher L Morton

  • 1Children's Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia.

Pediatric Blood & Cancer
|June 8, 2007
PubMed
Summary

Cisplatin shows significant antitumor activity in preclinical models of various childhood solid tumors. However, its effectiveness against acute lymphoblastic leukemia (ALL) xenografts was limited in this study.

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Area of Science:

  • Oncology
  • Pharmacology
  • Pediatric Cancer Research

Background:

  • Cisplatin is a cornerstone chemotherapy agent for adult and pediatric solid tumors.
  • Preclinical evaluation of cisplatin's efficacy against diverse childhood cancer models is crucial for treatment optimization.

Purpose of the Study:

  • To assess the antitumor activity of cisplatin against a comprehensive panel of childhood cancer xenografts.
  • To determine the in vitro and in vivo efficacy of cisplatin in models of solid tumors and acute lymphoblastic leukemia (ALL).

Main Methods:

  • Cisplatin was tested against 23 cell lines and 40 xenografts, including brain tumors, neuroblastoma, rhabdoid tumors, sarcoma, Wilms tumor, and ALL.
  • In vitro IC(50) values were determined, and in vivo antitumor activity was evaluated in mice using tumor growth delay and event-free survival metrics.

Main Results:

  • Cisplatin demonstrated broad in vitro activity with a median IC(50) of 0.87 microM.
  • Significant antitumor effects were observed in 20/28 solid tumor models, with objective responses in 25% of these models.
  • Limited efficacy was noted in acute lymphoblastic leukemia (ALL) xenografts, with no objective responses observed.

Conclusions:

  • Cisplatin exhibits substantial preclinical antitumor activity against a wide spectrum of solid tumor xenografts.
  • The observed preclinical activity aligns with the known clinical efficacy of cisplatin in solid tumors, while highlighting limited potential in ALL.
  • These findings support the continued use of cisplatin in solid pediatric malignancies and warrant further investigation for ALL treatment strategies.