Compound derived from Chinese tree bark can help treat pancreatic cancer

A new derivative of a compound found in the bark of a rare Chinese tree has powerful anticancer properties and a low toxicity profile, according to researchers at Roswell Park Comprehensive Cancer Center. Results of their study of the effects of the compound F118 in pancreatic cancer were published in the Journal of Experimental & Clinical Cancer Research

 

Image source: Google
Image source: Google

This type of cancer is particularly difficult to both treat and diagnose.

A lack of specific and accessible screening methods means that specialists often find the disease in its later stages, which can impact the patients’ outlook.

The ACS estimate that 12–14 per cent of people with early-stage pancreatic cancer go on to survive for 5 years.

New research offers much-needed hope; scientists have found that a derivative of camptothecin – which is a Chinese tree bark compound whose anticancer properties were discovered over half a century ago – can effectively kill pancreatic cancer tumours.

Fengzhi Li, Ph.D., who is an associate professor of oncology in the Department of Pharmacology and Therapeutics at the Roswell Park Comprehensive Cancer Center in Buffalo, NY, is the senior author of the new research.

Finding an effective, non-toxic compound

As Li and colleagues explain in their new paper, one of the main challenges of treating pancreatic cancer is the fact that the tumours are particularly dense, making it difficult for drugs to penetrate.

In the past, researchers have tried to use thousands of synthetic analogues of camptothecin in the fight against pancreatic tumours, but the Food and Drug Administration (FDA) have only officially approved two.

However, both of these derivatives target a protein that not only fuels the growth of tumours but is also key for the normal growth and renewal of tissue. Therefore, irinotecan and topotecan — the two FDA-approved camptothecin analogues — are highly toxic.

This is where Li and colleagues come in. In previous research, they developed another derivative of camptothecin that they called FL118, which they found to be effective against human colorectal cancer, as well as against head and neck cancer.

FL118 destroys drug-resistant tumours

Importantly, FL118 does not work by inhibiting the aforementioned key protein, which makes it a lot less toxic.

In this study, Li and team tested FL118 and found that the compound destroyed drug-resistant cancer cells and prevented tumours from spreading by destroying cancer stem cells.

They carried out both in vitro and in vivo experiments, wherein they used cancer cell cultures as well as human-derived pancreatic cancer tumours, which they applied to animal models.

The experiments revealed that, when used alone, FL118 effectively destroyed pancreatic tumours. When used together with the common chemotherapy drug gemcitabine, FL118 helped destroy tumours that had previously resisted treatment with either gemcitabine alone or FL118 alone.

Overall, the drug was well-tolerated and triggered none of the toxicity signs that irinotecan and topotecan produce.

“FL118’s high anticancer efficacy, along with its favourable toxicology profile, is consistent with the fact that this drug targets several key proteins involved in pancreatic cancer progression and treatment resistance,” says Li.

“Drugs that can more effectively reach and eliminate pancreatic tumours are urgently needed to treat this devastating disease,” he adds.

As Xinjiang Wang, co-corresponding study author, explains, “We believe that FL118 is promising new drug that can be further developed for the treatment of not only pancreatic cancer but also other types, such as colorectal cancer.”

“Our study provides strong support for the development of FL118-based therapies for pancreatic cancer, especially in patients who are resistant to current treatment,” said Wang.

Source: Medical News Today