Now Dr. Dewhirst and his team report that, in addition to sensitizing blood vessels to radiation, blockade of HIF-1 also impacts multiple aspects of tumor biology in a manner that depends strongly on the local environment of the tumor cells. For proximal tumor cells that are close to blood vessels and are therefore well oxygenated, HIF-1 is unlikely to be activated, and its inhibition will probably not have any effect. However, for distal tumor cells that are both oxygen starved and lacking access to nutrients because they are farther away from the tumor vasculature, HIF-1 inhibition may actually lead to significant resistance to radiation treatment.

HIF-1 inhibition is important because once solid tumors have grown to a certain size, the lack of oxygen (hypoxia) often suppresses their further growth. Unfortunately, many tumors adapt to this situation through the activation of a transcription factor that senses the low oxygen concentration and activates a series of genes which helps the tumor survive these conditions [HIF-1 (hypoxia-inducible factor 1)]. For example, there is evidence that activation of HIF-1 is able to alter the metabolism of tumor cells to use less oxygen. Furthermore, a number of other changes are linked to the activation of HIF-1, including increased breathing and dilation of blood vessels to increase oxygen supply and even the growth of new blood vessels into the tumor from the surrounding tissue (a process known as angiogenesis).

"If one hopes to optimize the combination of HIF-1-inhibiting and cytotoxic therapies, then, the strategy used should aim to maximize the effects of HIF-1 blockade on the vasculature while minimizing effects on the distal tumor cells. This could be achieved either through spatial or temporal selectivity of HIF-1 blockade," offers Dr. Dewhirst. This work may have important implications for the way in which HIF-1 inhibitors are used in the clinic with regards to identification of the types of tumors that are most likely to respond well to treatment and the optimal timing of combination chemotherapy and radiation therapy.

Sources:
News-Medicine.Net

Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity

Hey Richard! What's up? We miss you out here; I keep bringing my extension cord hoping to share the socket you, but don't know if you are ok or if you just found a new hangout. Well let me know or come by if you get a chance- I'll save you your table :-)