Anna Olivia Healey was born in 1996 and died of neuroblastoma at nine. Her name, shortened, now sits on an experimental pill: AOH1996.
City of Hope, the cancer center in Duarte, California, announced in October 2022 that a first patient had received the drug, the start of a phase 1 trial. Phase 1 is the earliest human stage. It asks how safe a drug is and what dose to use, not whether it cures anything.
A target nobody could hit
AOH1996 is a small molecule that blocks PCNA, short for proliferating cell nuclear antigen, a protein cells use to copy and repair DNA. Cancer cells lean hard on that machinery. The drug goes after a version of the protein called caPCNA, which shows up at high levels in tumor cells.
For years PCNA was written off. “No one has ever targeted PCNA as a therapeutic because it was viewed as ‘undruggable,’” said Long Gu, one of the paper’s lead authors at City of Hope.
What the lab work showed
The figure that matters most for now comes from animals. In a paper in Cell Chemical Biology, published in August 2023, the team reported results in mice carrying human neuroblastoma, breast cancer or small-cell lung cancer tumors. Treated mice had slower tumor growth than untreated ones, with the gap widening at around 30 days.
Pairing the drug with another chemotherapy agent, CPT-11, did better still. CPT-11 alone raised median survival in neuroblastoma mice by 34.6%. Add AOH1996 and the gain was 55.4%.
In dishes, the researchers treated human neuroblastoma cells for 18 hours with AOH1996 plus cisplatin. The combination left far fewer cancer colonies than cisplatin by itself, especially at higher cisplatin doses. Oncology Nursing News noted that in tests on over 70 cancer cell lines the drug killed cancer cells and left non-cancerous controls alone.
Where the money came from
The project has an unusual origin. Linda Malkas, then a faculty member at Indiana University’s medical school and now a professor at City of Hope, met Anna’s family as the girl neared the end of her illness. She walked Anna’s father through her research on proteins found only in cancer cells. He gave her a $25,000 check, aimed at neuroblastoma.
Caution from the clinic
When the mouse data came out, headlines ran ahead of the evidence. Amanda Brink, an oncology nurse practitioner, wrote that nurses should help patients see that phase 1 work is very early research. Results in the lab or in animals do not always carry over to people, she noted, and more human data are needed to judge whether AOH1996 works and what side effects it brings.
The oral pill is still in its phase 1 trial at City of Hope. Patients who want details can look up the study on ClinicalTrials.gov under the identifier NCT05227326.
Sources
- Latest Cancer Study Reveals Breakthrough: New Chemotherapeutic Agent Targets Multiple Solid Tumors | NAD
- Opinion: The Media May Have Oversold AOH1996, City of Hope's Pioneering Cancer Drug | Oncology Nursing News
