A research Group from the department of medical oncology of VU Medical Center, Cancer Center Amsterdam, headed by prof. Henk Verheul has identified a novel way in which tumors may become irresponsive to sunitinib.
Sunitinib is one of a group of recently developed anticancer agents, the so-called anti-angiogenic agents. These anticancer medicines act by inhibiting the formation of new blood vessels and thereby prevent tumors to grow. Sunitinib is a so-called receptor tyrosine kinase inhibitor (TKI) among others of the VEGF receptors, which is causing its anti-angiogenic effect and is an effective treatment for renal cell cancer. However, after some time unresponsiveness or resistance always occurs and the treatment has to be stopped.
The group of prof. Verheul has now identified a mechanism of resistance against sunitinib not described before. Based on measurements of sunitinib concentrations in tumors and continued exposure of tumor cells in the laboratory, they conclude that sunitinib in addition to its anti-angiogenic activity acts directly on tumor cell proliferation and induces a reversible type of resistance by sequestering the agent in intracellular vesicles, thereby decreasing its effectivity.
Based on these experiments, it is envisioned that after a treatment pauze tumors will become responsive to sunitinib re-treatment or that co-medication with agents that inhibit the intracellular storage capacity for sunitinib will further expand the possibilities of treatment of patients with renal cell cancer. This will be further investigated in follow-up studies.
Read the article which has been published this week in Clinical Cancer Research