Thread by @pashtoonkasi

What is the #CityOfHopeDrug?

A pill💊that can kill all #cancers.

I have been asked the "killer-pill" question several times this week. What is the hope or the hype?

Let’s learn together:
👇Here’s a tweetorial: @OncoAlert

Press release: August 1, 2023:
https://t.co/o5HNKEgIApcityofhope.org/city-hope-scie…

The study was published in the journal Cell Chemical and Biology.

"Small molecule targeting of transcription-replication conflict for selective chemotherapy."

Link to journal article:


It targets DNA🧬 replication/transcription simplistically speaking. https://t.co/5HEcipZRpVcell.com/cell-chemical-…

What did the authors @cityofhope find?

They have discovered/designed a new key🔑(inhibitor called AOH1996) for this particular lock🔒called PCNA (Proliferating cell nuclear antigen).

This molecule plays an important role in the formation and repair of DNA🧬.

Sequel to AOH1160.

In the paper, they report anti-tumor effects in 70 cell lines. However, to be specific, these were the following 9 cancers:

1. Leukemia
2. Lung
3. Colon
4. Brain
5. Melanoma
6. Ovarian
7. Kidney
8. Prostate
9. Breast

Also, xenograft experiments were done in mice/3 tumor types.

The new pill (AOH1996)💊 works on its own as well as sensitizes to this class of drugs called topoisomerase inhibitors. The latter is also involved in DNA 🧬damage/replication axis.

They also synergize with other drugs like cisplatin which are also considered DNA damaging.

One experiment of note, the drug actually didn't perform superior to one of the old chemotherapy drugs that we seldom use (CPT-11 or commonly called Topotecan).

The light blue line is the old chemo drug. It did better compared to the new pill (shown in red).
34.6%🆚11.5%.

What is my take?

I will just leave the final sentences from the authors themselves: copied/pasted:

"...We acknowledge that positive animal study results do NOT always translate into success in treating cancer patients. Future clinical studies are necessary..."

But I think the bigger issue is that this much hype to a pre-clinical study is not justified. Somewhat premature.

I am all about clinical trials and would I offer this new killer-pill as part of a trial to my patients? Absolutely✅.

Is it ready to cure all? No, unfortunately.