Combination bacteriolytic cancer therapy: Attacking cancer from inside out.
Extract: Problems associated with conventional cancer therapy are numerous, but two stand out: lack of specificity and the inability to totally eradicate all cancerous cells. The former leads to severe, sometimes intolerable, adverse effects, whereas the latter contributes to the dismal prognosis for a variety of cancer types. Effective cancer therapy should consist of components targeting both normoxic and hypoxic tumor tissues. The progression of solid tumors requires a sufficient blood supply to deliver both nutrients and oxygen. However, the growth rate of malignant tumors often outpaces angiogenesis. In addition, the tumor vasculature is often poorly organized and leaky in nature. Consequently, the oxygenation of tumor tissues is not uniform. Well-oxygenated tumor cells lie close to vascular elements, necrotic cells are far away, and a gradient of hypoxia lies in between. Confounding this complexity is the fact that the perfusion of tumors is dynamic, resulting in transiently hypoxic areas. Tumor hypoxia poses major problems for conventional cancer therapies, as radiation therapy and chemotherapy both rely on molecular oxygen and/or active replication of the target cells for their cytotoxic effects. Cancer cells in hypoxic areas are quiescent, making them resistant to such therapies. These cells can escape from the initial assault and start proliferating again once perfusion improves at a subsequent time, leading to relapse.
Zhou
Shibin
S
Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, MD 21231, USA.
Bettegowda
Chetan
C
Agrawal
Nishant
N