Cycle dude, thanks for the post with the article link in it. I’m glad they took a look HIF inhibition and radiation and the proper order to give them. They say that “radiation first” is best when attacking the tumor cells and the order doesn’t matter when attacking the tumor blood vessels. I’m not sure I understand their HIF blockade system which by itself did not appear to inhibit the tumor unlike our Panzem. When it comes to Panzem I still think it should be given first (especially when combined with other vascular targeting agents) but when combined with radiation, this article does not support this view but instead the opposite view. I will have to read it over a few times before I fully understand their work. I am glad they at least looked at the order of the treatments and found there was a difference in outcomes.
Aaron ______________________________
“…In contrast, our model of constitutive HIF-1 blockade also failed to show tumor growth restriction. To our knowledge, no prior studies have used siRNA to inhibit HIF-1a activity in vivo—the discrepancy here may, therefore, be methodological. Future work will need to be done to clarify whether HIF-1 inhibition by itself is an effective anticancer tool…”
“…This work may have important implications for the way in which HIF-1 inhibitors are used in the clinic. Our data suggest that HIF-1 blockade will be suboptimally effective if used prior to cytotoxic therapy. Although this sequencing may be a suitable approach for other antiangiogenic agents (Winkler et al., 2004 ), HIF-1 inhibitors might impede therapy if used this way. As an alternative, we propose that HIF-1 blockade should be used concurrently with chemotherapy and/or radiotherapy. One way to do so would be to administer HIF-1 blockade throughout the course of chemotherapy/radiotherapy, thereby maximally sensitizing the tumor vasculature. Alternatively, one could inhibit HIF-1 during breaks from treatment (e.g., over the weekend for fractionated radiotherapy or between cycles of chemotherapy), thereby minimizing the potential for interfering with their cytotoxicity…”
“It is also important to note that patient selection may play an eventual role in maximizing the potency of HIF-1 blockade. The mechanisms of radiation-induced HIF-1 activation are dependent on the presence of tumor hypoxia before treatment (Moeller et al., 2004 ). Therefore, methods of identifying tumors with high hypoxic fractions could be useful in selecting patients who will benefit from HIF-1 blockade during chemo/radiotherapy. Similarly, tumors found to have high HIF-1a expression levels may respond best to this type of treatment…”
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