Lapatinib

Lapatinib, a dual EGFR/HER2 tyrosine kinase inhibitor, reduced PKM2 expression in breast cancer cells. Mechanistically, EGFR activation induced nuclear translocation of PKM2. Lapatinib suppressed breast cancer cell proliferation by downregulating PKM2, which in turn decreased total STAT3 and phosphorylated STAT3 (Tyr705). PKM2 knockdown experiments confirmed that PKM2 regulates STAT3 expression. Thus, lapatinib inhibits proliferation partly through the PKM2‑STAT3 axis, revealing a novel nonglycolytic function of PKM2 in breast cancer.

Fig. 1 Pyruvate kinase type M2 is highly expressed in breast cancer tissues. (Guan M, et al., 2018)

This prospective phase 2a trial evaluated lapatinib (1250 mg/day, 6 months) in aggressive prolactinomas refractory to maximally tolerated dopamine agonists. Only 7 of 24 planned patients consented and 4 were treated. No patient met the primary endpoint (≥40% tumor dimension reduction), but three had stable disease (one with a 16.8% decrease). Prolactin responses were discordant. One patient with a prolactin‑secreting carcinoma progressed. Lapatinib was generally well tolerated (reversible grade 1 transaminitis, grade 2 rash, grade 1 bradycardia). The authors cautiously suggest that TKIs like lapatinib may be an option for difficult‑to‑treat aggressive prolactinomas.

Fig. 2 Effect of lapatinib therapy on tumor size. (Cooper O, et al., 2021)