Fox Chase Researchers Demonstrate Key Qualities of New Drug Candidate for Pancreatic Tumors

Dr. Astsaturov
A new study led by Igor Astsaturov, MD, PhD, published today in Molecular Cancer Therapeutics, demonstrates two key components necessary for a new drug candidate, LP-184, to effectively treat pancreatic adenocarcinoma.

PHILADELPHIA (August 8, 2023) — A new study led by Igor Astsaturov, MD, PhD, Co-Director of the Marvin & Concetta Greenberg Pancreatic Cancer Institute at Fox Chase Cancer Center, demonstrates two key components necessary for a new drug candidate, LP-184, to effectively treat pancreatic adenocarcinoma. The findings were published today in Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research.

Pancreatic adenocarcinoma is the second most common gastrointestinal cancer in the United States. It generally has a poor prognosis because it spreads quickly.

The research is part of a two-year collaboration between his lab and Lantern Pharma, said Astsaturov, who is also an Associate Professor in the Department of Hematology/Oncology at Fox Chase. Lantern is developing LP-184, a next generation acylfulvene-class therapeutic that acts as a tumor-site activated small molecule pro-drug. It is synthetically lethal in a broad spectrum of DNA damage repair (DDR)-deficient solid tumors.

Lantern Pharma is an artificial intelligence-driven company developing targeted cancer therapies and is launching a first-in-human phase 1A clinical trial of LP-184 as a single agent in advanced solid tumors.

“Lantern wanted to know what cancer types and genomically defined patient subsets would most likely benefit from the drug. That’s where we started collaborating,” said Astsaturov. This work has involved a number of colleagues from Fox Chase and researchers from Lantern Pharma.

He said that because researchers believe the molecule causes direct DNA damage, including double strand breaks, they began focusing their efforts on studying the activity of the drug in models that carried mutations in commonly altered components in the DDR pathway.

This work showed that the pathway was a critical component of the drug’s ability to provide tumor-selective efficacy because the activated molecule binds the DNA covalently, making cancers that are unable to repair DNA properly particularly vulnerable to LP-184.

This mechanism, called synthetic lethality, refers to a situation in which mutations in two genes together result in cell death but a mutation in either gene on its own does not.

Additionally, researchers found that LP-184 is a pro-drug that needs to be activated inside the cancer cells by a specific enzyme called prostaglandin reductase (PTGR1) that is often elevated in solid tumors but not in normal tissues.

“As part of this study, PTGR1 was genetically engineered in cell lines to either be present or absent, and the study showed that when cells lose PTGR1 they lose sensitivity to the drug,” said Astsaturov. “Based on our findings, we anticipate that LP-184 will expand therapy options to a large subset of patients with genetically defined pancreatic adenocarcinoma.”

Astsaturov said following this study and the recent investigational new drug clearance of LP-184 by the Food and Drug Administration, Fox Chase will soon launch a phase 1 clinical trial for LP-184 that will evaluate its safety and preliminary efficacy profile, as well as how the body responds to it.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence six consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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