The Great Debate

Apr 18, 2024

Here is our list for the top 10 Greatest Debates in history (feel free to weigh in):

1. Creation vs. Evolution
2. Free Will vs. Destiny
3. Nature vs. Nurture
4. Pen vs. Sword
5. The Chicken vs. the Egg
6. Albert Einstein vs. Niels Bohr
7. Lincoln vs. Douglas
8. Cats vs. Dogs
9. Idealism vs. Realism
10. Gore Vidal vs. William Buckley

Closer to home for EpicentRx is the debate between antiangiogenesis and proangiogenesis. According to the former, it is better to starve tumors to death with high doses of antiangiogenic therapies that deprive them of nutrients and oxygen. According to the latter, it makes more sense not to starve tumors to death but to stabilize and remodel the abnormal tumor vasculature, the better to increase oxygenation, immune cell access, and drug delivery.

On which side of this starve-vs.-feed-a-tumor debate is EpicentRx?

On both sides, really, which is not as wishy washy as it sounds.

At high doses the lead EpicentRx small molecule, RRx-001 (nibrozetone), is strongly antiangiogenic and shuts down the tumor vasculature, so if the intent is to use it as a single agent, which was the case in the Phase 1 first-in-human clinical trial, higher doses are better. However, at low doses, RRx-001 (nibrozetone) increases vessel dilation and blood flow, so if the intent is to use it in combination with other modalities like chemotherapy, immunotherapy, and/or radiation, then lower doses make more sense to improve drug and oxygen delivery.

Such are the cases in the ongoing Phase 3 clinical trial, REPLATINUM, for the treatment of small cell lung cancer (SCLC) and in the soon-to-start Phase 2b clinical trial, KEVLARx, for the treatment of head and neck cancer where low doses of RRx-001 (nibrozetone) are used to improve chemo- and radiosensitivity.

So, as RRx-001 (nibrozetone) demonstrates, when it comes to the treatment of tumors with anti- or proangiogenic agents, context most definitely matters.

Oh, by the way, just to settle this debate once and for all, the egg definitely came before the chicken.