paving the way for personalized therapy | fox chase cancer center - philadelphia, pa
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5/6/16, 7:55 AMPaving the Way for Personalized Therapy | Fox Chase Cancer Center - Philadelphia, PA
Page 1 of 3https://www.foxchase.org/blog/2016-04-19-paving-way-personalized-therapy
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Paving the Way for Personalized TherapyPOSTED ON TUESDAY, APRIL 19, 2016
By: Fox Chase Conversations
Fox Chase Cancer Center researchers have identified a wayforward for personalized cancer treatments for a widerange of cancers. Their findings can provide new insightinto the mechanisms of a small molecule andinvestigational new drug for cancer called ONC201. Thedrug not only stimulates a powerful anticancer protein
called TRAIL, but also the death receptor for TRAIL (also known as DR5) on tumor cells. Thisallows TRAIL to specifically kill tumor cells.
“We have revealed in unprecedented detail exactly how ONC201 works across a broad rangeof tumor types, and this has important clinical implications,” says senior study author WafikS. El-Deiry, MD, PhD, FACP, a medical oncologist and Deputy Director for TranslationalResearch at Fox Chase.
TRAIL is a promising anticancer protein because it prompts cell death in a wide range ofcancers while sparing normal cells, but its therapeutic benefit is limited because ofundesirable drug properties, such as a short half-life, difficult and expensive production, theneed for intravenous infusion, and poor penetration into certain tissues like the brain.
In the new study, the researchers analyzed gene activity and protein levels in nine tumortypes treated with ONC201, a drug given as a pill now being tested in clinical trials. El-Deiry’sgroup discovered that ONC201 triggers an increase not only in TRAIL, but also TRAIL
5/6/16, 7:55 AMPaving the Way for Personalized Therapy | Fox Chase Cancer Center - Philadelphia, PA
Page 2 of 3https://www.foxchase.org/blog/2016-04-19-paving-way-personalized-therapy
receptor abundance leading to tumor cell death throughthe integrated stress response that tumor cells normallyuse to survive. However, when overactivated by a druglike ONC201, the tumor cells are blocked from growingand/or are killed.
The new insight is that ONC201 pushes the integrated stress response too far, causing tumorcells to stop dividing and/or die. One protein in particular called ATF4 is stimulated andplays a critical role in ONC201’s anticancer activity. In essence, ONC201 delivers a doublewhammy to tumor cells, which may explain why it has such broad-spectrum anticanceractivity, El-Deiry explains.
Moving forward, the study has several clinical implications. Solid tumors or myeloma cellsthat normally create large amounts of protein during growth are predicted to be particularlysensitive to ONC201. The integrated stress response is often activated in these cells, andONC201 may push them over the edge.
The researchers are optimistic that their findings will lead to improved TRAIL-basedtherapies for individual cancer patients in the future.
For more information, please refer to the news release.
Congratulations! Congratulations! At the 2016 American
Association for Cancer Research (AACR) Annual
Meeting, the El-Deiry Lab tied MD Anderson
Cancer Center for first place with 21 abstract
submissions!
5/6/16, 7:55 AMPaving the Way for Personalized Therapy | Fox Chase Cancer Center - Philadelphia, PA
Page 3 of 3https://www.foxchase.org/blog/2016-04-19-paving-way-personalized-therapy
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