Opinion: The Media May Have Oversold AOH1996, City of Hope's Pioneering Cancer Drug

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

Early-phase clinical trials often involve medications that have not yet received their official names. Typically, these innovative drugs are given temporary names made up of a combination of numbers and letters while they are in development. Investigators seldom have the opportunity to determine the names of the drugs they work with.

The City of Hope Cancer Center, located in Duarte, California, recently had the unique opportunity to name one of its novel agents after a special patient. This drug, named AOH1996, is a tribute to the memory of Anna Olivia Healey, born in 1996.¹ Tragically, Anna passed away at the tender age of 9 due to neuroblastoma.²

Linda Malkas, PhD, who was a faculty member at Indiana University School of Medicine when she met Anna and her family, and is now a professor in the Department of Molecular Diagnostics and Experimental Therapeutics at City of Hope, sat down with Anna’s father when she was nearing the end stages of her disease, and shared with him her research on proteins unique to cancer cells. ³ Deeply inspired, Anna's father wrote a $25,000 check to fund Malkas' research, with a focus on neuroblastoma. Subsequently, Malkas and her team at City of Hope developed AOH1996, which is designed to target a protein found in all types of cancer.

In October 2022, City of Hope made an announcement that marked a significant milestone: the first patient had been treated with AOH1996 as part of a phase 1 clinical trial.⁴ More recently, investigators published the results of their pre-clinical research in Cell Chemical Biology.⁵ In their research, the scientists revealed the critical role of a protein known as Proliferating Cell Nuclear Antigen (PCNA) in the synthesis and repair of DNA within cells. Given that DNA damage stands as a hallmark of cancer development and growth, targeting PCNA, which plays a pivotal role in DNA repair, has emerged as a potentially effective therapeutic strategy against cancer. AOH1996, an oral drug, demonstrated its promise in animal studies by effectively inhibiting cancer cell growth. AOH1996 targets an isoform of PCNA known as caPCNA, which exhibits high expression levels in cancer cells. In extensive testing across more than 70 cancer cell lines, and in comparison to normal controls, AOH1996 exhibited the remarkable ability to selectively eliminate cancer cells while preserving non-cancerous cells.

When City of Hope's pre-clinical research was published in August 2023, the media quickly picked up on the news of this promising cancer drug. Given the profound impact that cancer has on so many individuals and their caregivers, any news of a promising cancer drug is welcome. Naturally, patients and caregivers will inquire about this drug and oncology nurses are often a trusted source of information for answers to patient’s questions about emerging therapies. Oncology nurses are also typically the first point of contact for patients who reach out to their oncologists through electronic communication. Therefore, it is important for oncology nurses to have a comprehensive understanding of what is currently known about AOH1996 and where this drug is in its development.

What does this mean for patients and nurses?

AOH1996 is currently being tested in a phase 1 clinical trial at City of Hope. This means it is being tested in a small number of patients to obtain additional information regarding the safety profile of the drug and determine optimal dosing. If patients are interested in finding out more about participating in this clinical trial, they can visit the study’s page on ClinicalTrials.gov (NCT05227326).⁶

Unfortunately, success in treating cancer cells in the laboratory or in animal studies does not always lead to success in treating human patients within clinical trials. Additional results from human studies are needed to determine AOH1996’s efficacy as a cancer treatment and to better establish its side effect profile.

As investigators continue their study of AOH1996, we can only hope that patients will experience benefits from this drug and witness their cancer respond positively to it. This progress would further propel AOH1996 through the drug development process, hopefully ultimately granting it an official drug name. This will hopefully allow researchers another distinctive way to honor Anna and her enduring legacy with a drug that becomes widely recognized and brings benefits to many future patients.

References

1. Logsdon Z. Cancer center announces first patient has received City of Hope’s novel, potentially cancer-stopping pill.” News release. City of Hope. October 19, 2022. August 22, 2023. www.cityofhope.org/cancer-center-announces-first-patient-has-received-city-hopes-novel-potentially-cancer-stopping
2. Researcher Linda Malkas on Inspiration and Innovation. News release. City of Hope. September 30, 2022. Accessed September 13, 2023. www.cityofhope.org/researcher-linda-malkas-inspiration-and-innovation
3. Linda Malkas, Ph.D. City of Hope. Accessed September 13, 2023. www.cityofhope.org/linda-malkas.
4. Logsdon, Zen. “Cancer Center Announces First Patient Has Received City of Hope’s Novel, Potentially Cancer-Stopping Pill.” City of Hope, 19 Oct. 2022, www.cityofhope.org/cancer-center-announces-first-patient-has-received-city-hopes-novel-potentially-cancer-stopping.
5. Gu L, Li M, Li CM, et al. Small molecule targeting of transcription-replication conflict for selective chemotherapy. Cell Chem Biol. 2023;S251-9456(23)00221-0.doi:10.1016/j.chembiol.2023.07.001
6. AOH1996 for the treatment of refractory solid tumors. ClinicalTrials.gov identifier: NCT05227326. Updated August 18, 2023. Accessed September 13, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05227326