Researchers at The Wistar Institute and the University of South Florida have advanced a novel compound that specifically targets the endoplasmic reticulum (ER) stress response that is frequently hyperactivated in cancer and promotes survival of cancer cells during stressful conditions. The new compound has unique chemical properties that allow for precise activation and can be used for tracking its activity in vivo thanks to the emission of fluorescence.
Research was published online in the Journal of Medicinal Chemistry.
The ER is a cellular structure that oversees protein folding and assembly, and it activates stress response mechanisms in response to the accumulation of misfolded proteins or other stressful conditions, including low oxygen.
“Certain cancers rely on the protective role of the ER stress response to sustain their growth in stressful environmental conditions,” said Chih-Chi Andrew Hu, Ph.D., associate professor in Wistar’s Immunology, Microenvironment & Metastasis Program, and co-lead author on the study with Juan R. Del Valle, Ph.D., from the University of South Florida. “We and other groups showed that genetically and pharmacologically targeting the ER is a very effective way to attack various tumors.”
The Hu lab has been actively advancing a research program for development of compounds to block vital functions of the ER stress response, specifically inhibitors of the IRE1 protein that senses the ER stress and responds by activating a cascade of cellular events. In addition to inducing tumor cell apoptosis, these compounds activate antitumor T-cell function and inhibit tumor-associated immunosuppressive cells in vivo in mouse models, resulting in tumor shrinkage.
“This class of inhibitors has shown therapeutic promise in several cancer types, including chronic lymphocytic leukemia and Burkitt lymphoma,” said Hu. “Therefore, we are very interested in advancing them to the clinic.”
In this study, through a series of chemical modifications, Hu and collaborators created a molecule called PC-D-F07 that is pharmacologically inactive and requires UV irradiation to be “turned on” and converted into the active D-F07, which is a very potent inhibitor of IRE-1 function.
The novel prodrug strategy enhances the efficacy of IRE-1 inhibitors and allows fine control of their activity at a precise time and location by UV irradiation. Importantly, once active, D-F07 emits fluorescence that can be tracked in cells and potentially in vivo, providing a real-time therapy readout. This new strategy for stimulus-mediated release of pharmacological activity provides a promising platform to target the ER stress response for anticancer therapy and for developing other potent inhibitors.
The Latest on: Cancer treatment
[google_news title=”” keyword=”cancer treatment” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Cancer treatment
- Dr. Roach: The best treatment for radiation injury proves to be APCon September 27, 2023 at 9:02 pm
APC delivered by a colonoscope or sigmoidoscope is often considered the most effective treatment, but your experience shows that it’s not always easy to choose the best treatment. Sometimes multiple ...
- Steve Scalise provides update on cancer treatmenton September 27, 2023 at 7:54 pm
It's been one month since Congressman Steve Scalise announced his cancer diagnosis. The Majority leader says he is following his doctor's advice for an aggressive treatment plan. He announced in ...
- Local support group hosts spa day for cancer patientson September 27, 2023 at 6:01 pm
September is ovarian and uterine cancer awareness month. Doctors are teaming up with a local support group to make a group of patients feel special before the month is over.
- Scalise returns to government spending fight amid cancer treatmenton September 27, 2023 at 1:45 pm
House Majority Leader Steve Scalise (R-LA) returned to Capitol Hill this week after receiving cancer treatment, meeting with other GOP leaders as lawmakers scramble to avert a government shutdown just ...
- House Majority Leader Steve Scalise gives update on his cancer treatmenton September 27, 2023 at 1:06 pm
"The good news is the cancer has dropped dramatically because of the success of the chemotherapy attacking the cancer," Scalise said.
- Ed Davey promises legal guarantee on cancer treatment starting time during conference speechon September 26, 2023 at 8:18 am
Sir Ed began his address by poking fun at the Tory government, saying ‘clown’ is the ‘wrong C-word’ for the Conservatives ...
- Lib Dems pledge two-month cancer treatment guaranteeon September 26, 2023 at 7:38 am
The Liberal Democrats have proposed a new legal right to get cancer treatment within two months of an urgent referral in England. The party said in the last year more than 72,000 people waited longer ...
- New target identified for pancreatic cancer treatmenton September 26, 2023 at 6:13 am
Researchers have found a protein to block the growth of cancer stem-like cells as a possible treatment for pancreatic cancer.
- Boy's cancer treatment fund reaches £200kon September 26, 2023 at 2:04 am
Teddy Lichten,4, was diagnosed with high-risk neuroblastoma in July 2022.
- Hassocks boy's cancer treatment fund reaches £200kon September 26, 2023 at 2:04 am
The mother of a four-year-old boy from West Sussex said it was "really exciting" to have raised £200,000 for potentially life-saving cancer treatment. Teddy Lichten, from Hassocks, was diagnosed with ...
via Bing News