neoangiogenesis in general. Interestingly, 1 year of postoperative adjuvant treatment with the TKI imatinib
was found to improve disease-free survival signicantly
in a dierent type of tumour, gastrointestinal stromal
tumours (GIST).10 In the context of this rare but
instructive tumour type, TKI treatment has been shown
to induce cellular quiescence in tumour cells, hence
providing a survival benet to the patient by slowing
down tumour cell growth kinetics.11 This appears not to
be the case in renal-cell carcinoma. Instead, we believe
that the results of Haas and colleagues study might well
be in line with the angiogenic switch model proposed by
Judah Folkman in the 1990s.12 The underlying idea is that
tumours are independent of blood vessel formation up
to a certain size and that neoangiogenesis permits the
growth of larger tumours. Hence, only larger tumour
nodules will contain topological areas that are critically
dependent on neoangiogenesis and therefore sensitive
to VEGF-targeting agents. Why sunitinib or sorafenib
did not prevent this switch is unknown. However, other
mechanisms of neoangiogenesis that can compensate
for VEGF deprivation have been reported.12 Although
outside the scope of the present study, it will be
important to establish whether TKI-treated and placebotreated patients show dierences in their responses
when re-challenged with TKIs after disease recurrence.
Although VEGF-targeted TKIs haven been shown to
be ineective in the adjuvant setting in high-risk renalcell carcinoma in the present study,6 future approaches
might focus on pathways to eliminate hidden tumour
cells. Harnessing the immune system would be an
attractive opportunity, together with eorts to nd cell
surface markers that can be used to trace and target
dormant renal-cell carcinoma cells.
As much as we hoped for a more positive outcome
for the use of adjuvant VEGF-targeted TKIs in renal-cell
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Mohammed Huwais
Comment
Comment
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