Transient anti-angiogenic treatment improves delivery of cytotoxic compounds and therapeutic outcome in lung cancer
Menée à l'aide d'une tomographie par émission de positrons sur un modèle murin de cancer du poumon non à petites cellules, cette étude met en évidence les effets, sur le réseau vasculaire tumoral, d'un traitement anti-angiogénique de courte durée par un inhibiteur de VEGFR/PDGFR appelé PTK787
Extensive oncologic experience argues that the most efficacious applications of anti-angiogenic agents rely upon a combination with cytotoxic drugs. Yet there remains a lack of clarity about how to optimize scheduling for such drug combinations. Prudent anti-angiogenic therapy might transiently normalize blood vessels to improve tumor oxygenation and drug exposure. Using [15O]H2O Positron Emission Tomography (PET) imaging in a preclinical mouse model of non-small cell lung cancer, we observed that short-term treatment with the VEGFR/PDGFR inhibitor PTK787 licensed a transient window of improved tumor blood flow. The improvement observed was associated a reduced leakiness from tumor vessels, consistent with induction of a vascular normalization process. Initiation of a cytotoxic treatment in this window of tumor vessel normalization resulted in increased efficacy, as illustrated by improved outcomes of erlotinib administration after initial PTK787 treatment. Notably, intermittent PTK787 treatment also facilitated long-term tumor regression. In summary, our findings offer strong evidence that short-term anti-angiogenic therapy can promote a transient vessel normalization process that improves the delivery and efficacy of a targeted cytotoxic drug.