A new study, published in the Journal of Experimental & Clinical Cancer Research, finds that a synthetic analog of a compound found in a rare Chinese tree can be used to tackle treatment-resistant pancreatic cancer.
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.
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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 tumors.
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.
As Li and colleagues explain in their new paper, one of the main challenges of treating pancreatic cancer is the fact that the tumors are particularly dense, making it difficult for drugs to penetrate.
In the past, researchers have tried to use thousands of synthetic analogs of camptothecin in the fight against pancreatic tumors, 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 tumors but is also key for the normal growth and renewal of tissue. Therefore, irinotecan and topotecan — the two FDA-approved camptothecin analogs — 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.
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 tumors 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 tumors, which they applied to animal models.
The experiments revealed that, when used alone, FL118 effectively destroyed pancreatic tumors. When used together with the common chemotherapy drug gemcitabine, FL118 helped destroy tumors 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 favorable 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 tumors 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.”