Scientists at OncoDxRx have unveiled a class of drug known as Avagacestat as a promising new target for future lung cancer treatments using a drug screening process based on patient’s own gene expression signature obtained from their plasma samples – PGA (Patient-derived Gene expression-informed Anticancer drug efficacy).

The study involved the screening of over 700 approved drugs. PGA employed a patient-derived gene expression signature, allowing scientists to analyze and match the pattern of the disease with corresponding drugs. The team identified a drug among others, avagacestat, a drug previously used to treat Alzheimer’s disease, that was predicted to show high patient response rate. This finding highlighted γ-secretase activity as a vulnerability that may be targetable in most lung cancer.

The discovery of secretase’s role in fueling lung tumor growth opens new possibilities for targeted therapies. The γ-secretase inhibitors, a class of small-molecule compounds that target the Notch pathway, have been shown to elicit a response in some tumors as single agents and sensitize non-small-cell lung cancer (NSCLC) to cytotoxic and targeted therapies. Many of the γ-secretase substrates are directly involved in carcinogenesis or tumor progression, and are ideal candidates to be the "on-target" biomarkers for γ-secretase inhibitors.

Despite the promising results, avagacestat is unlikely to be directly used for treating NSCLC due to its known side effects. Nevertheless, OncoDxRx’s scientists intend to use avagacestat as a starting point of PGA assay for guiding drug discovery, development and repurposing, envisioning optimization of the compound’s properties, such as potency and safety, to create a more effective and safer therapeutic option for lung cancer patients.