Phase 1 Clinical Trial AOH1996 for the Treatment of Refractory Solid Tumors

The City of Hope-developed small molecule AOH1996 targets a cancerous variant of the protein PCNA. In its mutated form, PCNA is critical in DNA replication and repair of all expanding tumors. Here we see untreated cancer cells (left) and cancer cells treated with AOH1996 (right) undergoing programmed cell death (violet). (Photo credit: City of Hope)

This particular clinical trial for solid tumours has been widely reported in the news this week (July/august 2023). It is touted as a “cancer-killing pill” has appeared to “annihilate” solid tumours in early research – leaving healthy cells unaffected.  Whether these are the words of the sponsor or the media is not clear. Some of the media wording may have been based on preclinical data on animal testing. The new drug has been in development for 20 years and been undergoing pre-clinical research in the US.  

How does it work?

Known as AOH1996, it targets a cancerous variant of a protein called proliferating cell nuclear antigen (PCNA).  In its mutated form, PCNA is “critical” in the replication of DNA, and the repair of all “expanding tumours”. 

The lead researcher, Dr LInda Malkas, believes that proliferating cell nuclear antigen (PCNA), which plays an essential role in the replication and repair of cells, would be a less toxic cancer therapy that targets mutated cancer cells while leaving normal cells alone. The treatment has been shown in preclinical research to target PCNA and inhibit the growth and spread of a broad range of human cancer cells. The research protocol notes that AOH1996 is not toxic to healthy cells and that treatment with this medicine both pauses cell DNA synthesis and inhibits DNA repair, leading to a type of cell death known as apoptosis in the cancer cells.  

Why is it called AOH1996?

The drug name AOH1996 derives Anna Olivia Healy, who was born in 1996 and died in 2005 from a deadly neuroblastoma aged just nine. Dr Linda Malkas, who leads the research team, met Anna’s father just before she died and was inspired to find a cure in her memory.

What does this mean for Neuroendocrine Neoplasms (NENs)?

All NENs (NET and NEC) are solid tumours. There is no indication yet that this will work for any of these tumours, particularly low-grade NETs which don’t have a great track record of responding to chemotherapy.  However, until we have further information and data, no one really know for sure. 

According to media reports, the researchers have tested AOH1996 in more than 70 cancer cell lines (i.e. in a laboratory not on humans). They found the molecule selectively kills cancer cells by disrupting the normal cell reproductive cycle.  I could not see any specific mention of “Neuroendocrine”.  I did find mention of small cell lung cancer which is known to predominately be a Lung Neuroendocrine Carcinoma. 

Worth noting the trial is very small.  According to the clinical trial document (see below), estimated to be around 8 participants and commenced October 2022, due completion end of March 2024. The chances of there being someone on the trial with a NEN are pretty slim I suspect. 

I will keep this blog post live. This drug development is in its very early stages. 

Clinical Trials Document

The AOH1996 human trial is being managed by City of Hope, one of America’s largest cancer research and treatment organisations.  It is sponsored by US NIH.  A second site in Arizona is listed in the clinical trials document.

The trial commenced August 2022 and has an estimated enrolment of 8 participants. The first patient was dosed in October 2022.  Eligible patients include adults with solid tumors who have not found standard treatments effective. Participating patients will be asked to take the medication in pill form twice a day. 

Click here to read the clinical trials document.


I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. 

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.   

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

General Clinical Trials Disclaimer

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact.  If you need questions, the articles here is very useful Questions to Ask About Clinical Trials | Cancer.Net

The inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan. 



Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product.  Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document  Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET

Thanks for reading.


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