Oncology Medical News about lapatinib, SN-38, cancer cells

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The dual EGFR/HER-2 tyrosine kinase inhibitor lapatinib sensitizes colon and gastric cancer cells to the irinotecan active metabolite SN-38
International Journal of Cancer, 08/12/09

LaBonte MJ et al. - In a study to evaluate the therapeutic potential of lapatinib, alone and in combination with SN-38 in colon and gastric cancer cell lines, these results provide compelling preclinical rationale indicating lapatinib to be a potentially efficacious chemotherapeutic combination partner for irinotecan in treatment of gastrointestinal carcinomas.

Methods

Lapatinib is a dual tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) and HER-2.
This study evaluated the therapeutic potential of lapatinib, alone and in combination with SN-38, the active metabolite of irinotecan (CPT-11), in colon and gastric cancer cell lines.

Results

Concentration-dependent antiproliferative effects of both lapatinib and SN-38 were observed in all colon and gastric cancer cell lines tested but varied significantly between individual cell lines.
Lapatinib potently inhibited growth of a HER-2 overexpressing gastric cancer cell line and demonstrated moderate activity in gastric and colon cancer cells with detectable HER-2 expression.
Combination lapatinib and SN-38 interacted synergistically to inhibit cell proliferation in all colon and gastric cancer cell lines tested.
Cotreatment with lapatinib and SN-38 also resulted in enhanced cell cycle arrest and induction of apoptosis with subsequent cellular pharmacokinetic analysis, demonstrating that lapatinib promoted the increased intracellular accumulation and retention of SN-38 vs SN-38 treatment alone.
Combination lapatinib and CPT-11 demonstrated synergistic antitumor efficacy in the LoVo colon cancer mouse xenograft model with no apparent increase in toxicity vs CPT-11 monotherapy.

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