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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...
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...

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Related Experiment Video

Updated: Jun 22, 2026

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

Initial testing (stage 1) of lapatinib by the pediatric preclinical testing program.

Richard Gorlick1, E Anders Kolb, Peter J Houghton

  • 1The Children's Hospital at Montefiore, Bronx, New York 10467, USA.

Pediatric Blood & Cancer
|June 26, 2009
PubMed
Summary

Lapatinib showed limited efficacy in pediatric cancer models, with in vitro activity at high concentrations. This suggests differences in EGFR/ErbB2 targeting applicability between adult and pediatric cancers.

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Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Lapatinib is a reversible tyrosine kinase inhibitor targeting EGFR and ErbB2.
  • It demonstrates in vitro and in vivo activity against adult cancer cell lines and efficacy in ErbB2-overexpressing breast cancer.

Purpose of the Study:

  • To evaluate the efficacy of Lapatinib in pediatric cancer models.
  • To assess Lapatinib's activity against a panel of pediatric cancer cell lines and xenografts.

Main Methods:

  • Lapatinib was tested in vitro against the PPTP cell line panel (1.0 nM to 10.0 microM).
  • In vivo studies involved oral administration to PPTP xenografts (160 mg/kg twice daily for 6 weeks).
  • Pharmacokinetic parameters were determined in scid(-/-) mice.

Main Results:

  • The median IC50 for Lapatinib was 6.84 microM against the cell line panel.
  • Lapatinib was well tolerated in vivo with minimal toxicity (1.5%).
  • Limited efficacy was observed in xenografts, with no objective responses in solid tumor or ALL panels.

Conclusions:

  • Lapatinib demonstrated limited activity in the studied pediatric xenograft models.
  • In vitro activity was observed at concentrations exceeding specific EGFR/ErbB2 inhibition levels.
  • Findings suggest potential fundamental differences in EGFR family member therapeutic targeting between adult and pediatric cancers.