AACR 2017 | Poster 155/22 – Addition of RP6530, a dual PI3Kδ/γ inhibitor, accentuates romidepsin activity in Non-Hodgkin Lymphoma cells in vitro

This year’s American Association for Cancer Research (AACR) annual meeting took place on 1–5 April in Washington, DC, USA. The program committee Chair was Kornelia Polyak, MD, PhD, from the Dana-Farber Cancer Institute, Boston, Massachusetts.

On Sunday 2^nd April, a poster (155 / 22) by Srikant Viswanadha, from Incozen Therapeutics Pvt. Ltd, et al. titled “Addition of RP6530, a dual PI3Kδ/γ inhibitor, accentuates Romidepsin activity in NHL cells in vitro” was presented.

The group evaluated the combination of romidepsin and RP6530, a potent and selective dual PI3Kδ/γ inhibitor, in multiple NHL cell lines: OCI-LY-1, OCI-LY-10, RAJI, DAUDI, TOLEDO, JEKO, MAVER, and SU-DHL-1.

Key Highlights:

• Synergism/additivity between RP6530 and romidepsin for anti-proliferative activity was observed in all tested cell lines
• The combination was most efficacious in JEKO, OCI-LY-1, OCI-LY-10, and SU-DHL-1 cells
• Incubating cells with 3–5nM romidepsin and 3 or 5μM RP6530 resulted in a 2–5-fold increase in total apoptotic population
• Romidepsin (1–5nM) and RP6530 (1–5μM) induced a G0/G1 arrest (2–3-fold) with a corresponding increase in apoptotic cell percentage
• Treatment with RP6530 reduced pAKT expression by 40–90% across cell lines
• Romidepsin plus RP6530 enhanced expression of cleaved PARP (8–60-fold) versus either agent alone

The poster concluded by stating that adding RP6530 increased the activity of romidepsin in NHL cells. This provides a rationale for using this combination in future clinical trials with newly diagnosed or relapsed NHL patients, as it presents a potentially safer alternative to current therapy.