Treatment of non-small cell lung cancer NSCLC, the leading cause of cancer-related death, relies heavily on radiation therapy, which however is frequently compromised by development of radioresistance. HypOxystation users Jiang et al. of the University of Oxford describe their study of olaparib, an inhibitor of Poly(ADP-ribose) polymerase 1 (PARP-1) which serves to enhance radiosensitivity, to treat lung carcinoma at hypoxia and normoxia ("Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality"; Int J Radiation Oncol Biol Phys, Vol. 95, No. 2, pp. 772e781, 2016). The lab uses a Don Whitley H35 HypOxystation to create stable, contiguous hypoxic conditions for their cell culture.

A combination of olaparib and radiation significantly increased DNA double strand breaks, and at hypoxia (1% oxygen), the radiation-sensitizing effect of olaparib was increased relative to normoxia (21% oxygen), as evidenced by a decrease in clonogenic survival rates. In vivo effects of oxygen availability were examined in subcutaneous Calu-6 and Calu-3 xenograft assays, where Calu-6 tumors comprise extensive hypoxic areas, and assays focusing on RAD51 protein expression showed that homologous recombination was considerably impacted by olaparib, specifically in hypoxic regions. CC3 staining of Calu-6 tumors as a measure of apoptosis also showed that hypoxic areas are more severely impacted by the combination of olaparib and radiation than normoxic areas. CA9 immunostaining served as a marker for hypoxia.

In Jiang’s study, the hypoxic microenvironment is obviously mediating a “contextual synthetic lethality” of the PARP inhibitor olaparib in conjunction with hypoxia-induced recombination defects that impair DNA DSB repair. Thus, the authors suggest a combination therapy for NSCLC, and other radioresistant hypoxic tumors such as squamous carcinoma, consisting of PARP-1 inhibitors and radiation. The physiological atmosphere created inside the HypOxystation will be essential in further examining the underlying effects of the hypoxic tumor microenvironment and the mechanisms by which proliferating cancer cells are sensitized to radiation treatment. The Don Whitly Scientific HypOxystation boasts a very low gas consumption (3.5 L of nitrogen gas/24 hour period) due to its gas-tight build and extremely accurate gas control.