ONC201 Suppresses Growth Among Various Breast Cancer Cell Types

November 6, 2015

PHILADELPHIA (November 6, 2015) – A recent preclinical investigation of a novel small molecule called ONC201 suggests it could potentially offer therapeutic benefits for patients diagnosed with either triple negative or non-triple negative breast cancer. Researchers at Fox Chase Cancer Center – Temple Health presented these findings at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston from
Nov. 5-9, 2015.

Wafik S. El-Deiry, MD, PhD, FACP, Professor of Medical Oncology, Deputy Cancer Center Director, and Co-Program Leader in Molecular Therapeutics at Fox Chase, said the research conducted in his lab investigated ONC201 to test if the molecule had the ability to kill breast cancer cells. The findings indicate that ONC201 induces cell death, with activity against both triple negative and non-triple negative breast cancer cell lines, including BRCA1-deficient cells. ONC201 is a first-in-class small molecule compound being developed in the clinic by Oncoceutics, Inc. in Hummelstown, Pa, who collaborated on the research.

“The interesting result in our research is that ONC201, which is a first-in-class cell death pathway inducer, has activity in non-triple negative breast cancer cells. That’s an exciting observation that was not necessarily predictable,” El-Deiry said. “The compound stimulates a signaling pathway [the TRAIL pathway] within the tumor cells that signals them to die.”

The compound has been used in previous clinical trials in patients with solid tumors, but no clinical trials have specifically targeted breast cancer. ONC201was recently investigated in a first-in-man phase 1 clinical trial in advanced solid tumors that showed its safety, pharmacokinetics, and recommended phase II dose. ONC201 also has been shown effective against pediatric non-Hodgkin’s lymphoma as single therapy and in combination with other agents. Its efficacy is under investigation for other types of tumors.

El-Deiry and his colleagues’ research investigated ONC201 efficacy in TRAIL-sensitive and TRAIL-resistant breast cancer cells. The TRAIL pathway, considered an important target for cancer therapy, selectively kills cancer cells. Only a subset of triple negative breast cancers is sensitive to TRAIL, but other breast cancer molecular subtypes are highly resistant, such as non-triple negative breast cancer cell lines, including HER2 and estrogen receptor-positive.

A single dose of ONC201 was well tolerated and effective in vivo in the triple-negative breast cancer xenograft model used in the trial.

The findings suggest ONC201 “exerts cytotoxic effects against a broad range of breast cancer cells … and these effects are observed regardless of the TRAIL sensitivity of the cells,” El-Deiry said.

“We would hope that the type of research we are doing in various types of breast cancer may help indicate which patients to include in clinical trials,” El-Deiry said.

His lab is now investigating the signaling in the cells that would explain the sensitivity of the compound.

“We are working on in vivo studies to show the effects of the compound as a single agent, and we are already working on various combinations of other agents with the compound,” El-Deiry said. “As we learn more about ONC201, it seems to be active and potent. We look forward to continuing to work on it and to shape clinical trials in this area.”

Fox Chase researchers Marie D. Baumeister, Jessica Wagner, Christina L.B. Kline and David T. Dicker were involved with this study, as well as Joshua E. Allen, of Oncoceutics, Inc.

Financial Disclosures:

Dr. El-Deiry's laboratory research on ONC201 at Fox Chase Cancer Center is supported by grants from the National Institutes of Health and the American Cancer Society. As a founding partner, Dr. El-Deiry has a financial stake in Oncoceutics and ONC201; however, Fox Chase Cancer Center has no financial ties to the company.


The Hospital of Fox Chase Cancer Center and its affiliates (collectively “Fox Chase Cancer Center”), a member of the Temple University Health System, is one of the leading cancer research and treatment 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 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 five 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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