Easy as P.I.E.

Mar 1, 2024


For tumors, unfortunately, to not only survive but also thrive is often as easy as p.i.e.—those letters are an acronym for the three steps of persuasion, invasion, and evasion.

Step 1 for tumor cells is to persuade—they must coerce stromal or non-cancerous cells to switch sides and support their growth over that of normal tissues.

Step 2 is to invade—this is the process whereby cancer cells break free from the main tumor mass and spread not only to surrounding tissues but also to circulatory or lymphatic vessels which carry them to distant organs for establishment of metastases.

Step 3 is to evade—tumors must counteract the immune response or risk elimination. They evade through masquerade—by disguising themselves as normal, healthy cells so that any immune response completely bypasses them.

It is the job of lead EpicentRx therapies, AdAPT-001, and RRx-001 (nibrozetone) to make tumors eat humble p.i.e.—in this context the ‘p’ stands for precipitate, ‘i’ stands for immune response, and ‘e’ for eliminate, as these therapies can precipitate an immune response for the elimination of tumors most often in combination with other anti-cancer agents.

The step-by-step recipes for humble p.i.e. are hopefully found in ongoing or soon-to-start EpicentRx clinical trials. For AdAPT-001, this is the Phase 2 clinical trial called BETA PRIME where AdAPT-001 is given with a checkpoint inhibitor to treat resistant sarcomas. For RRx-001 (nibrozetone), this is the Phase 3 clinical trial, REPLATINUM, where RRx-001 is administered to sensitize platinum-resistant small cell lung cancer (SCLC) to platinum-based chemotherapy; this is also the soon-to-start Phase 2b trial called KEVLAR where the administration of RRx-001 (nibrozetone) may prevent or mitigate against severe oral mucositis, a debilitating complication that commonly develops during the treatment of head and neck cancer with chemotherapy and radiation.