New findings published in Nature Chemical Biology show promise for finding new solutions to treat lung cancer and other deadly diseases. Kentucky continues to lead the nation in incidence and death rates from lung cancer, and the University of Kentucky is committed to reducing these numbers.
According to the National Cancer Institute, cancer is among the leading causes of death worldwide. And of those diagnosed in the United States, lung cancer accounts for 25 percent of cancer deaths. The numbers are sobering: one out of every two patients diagnosed with lung cancer won’t survive past 12 months.
In an effort to combat this problem, a collaboration between scientists from University of Kentucky College of Pharmacy, Memorial Sloan Kettering Cancer Center, and St. Jude Children’s Research Hospital brings researchers one step closer to a solution.
A compound developed by Dean Kip Guy’s lab of UK College of Pharmacy, with research that began at St. Jude Children’s Research Hospital, now provides us with a way to block cancer-causing proteins on a cellular level.
The groundwork began more than 10 years ago when Dr. Bhuvanesh Singh, a physician-scientist at Memorial Sloan Kettering Cancer Center, identified that an increase of a protein called DCN1 led to more malignant lung cancers and shorter life spans for his patients. Of the patients he studied, those with high levels of DCN1 succumbed to the disease more quickly than those with normal levels.
Frustrated by their findings, Singh’s team set out to study the specifics of DCN1. While DCN1 is a normally occurring protein, his team found that too much of it leads directly to cancer formation. Simply put, a malignant tumor was formed when the amount of DCN1 in a cell was increased. Thus, patients with more DCN1 got sick more quickly and died faster than their counterparts.
Efforts in Brenda Schulman’s lab at St. Jude, led by biochemist Daniel Scott, established how DCN1 interacts with other proteins and controls cellular processes. Their key discovery used X-ray crystallography to show that a small modification of the partner protein to DCN1, known as UBE2M was required for DCN1 to work. This modification, N-terminal acetylation (while common) had not previously been shown to be critical to controlling activity of this specific protein. Recognizing the potential for targeting this modification, Schulman reached out to form a collaboration between the three laboratories.
Their goal: to develop a way to stop DCN1 from killing patients.
Understanding the behavior and function of DCN1 was far more ambitious than running simple tests. It was a significant step forward in understanding how proteins within a cell work.
Building upon the science from Schulman’s team, Jared Hammill from Guy’s lab and Danny Scott from Schulman’s lab worked to stop the interactions of DCN1 all together. If DCN1’s activity depended on this interaction, then it stood to reason they could create a compound to intervene and stop the interaction from happening.
Guy describes the interaction as a “lock and key model.” Scientists have a blank key—which is UBE2M—and a lock, which is DCN1. The key wants to fit into the lock so it’s modified until it fits. This modification process is N-terminal acetylation.
“What’s the significance?” Guy said. “Well, we’re the first people to show that protein interaction controlled by N-terminal acetylation can be blocked. We’re essentially jamming the lock with a compound so the key won’t fit.”
The items jamming that lock are a series of small molecules created in the lab. When the molecules were tested directly in cancer cells, they worked. They effectively blocked DCN1 from binding to UB2EM. After decades of collaborative research, there was finally a barrier between lock and key.
The impact of these findings for healthcare and lung cancer patients specifically could be profound.
“We are excited about the implications of this research, which offer us a meaningful solution for addressing diseases like cancer, neurodegenerative disorders, and infection,” Schulman said. “It’s exciting to collaborate with so many complementary groups of expertise and to watch how Dr. Scott and Dr. Hammill led the team. This research opens many new doors for us.”
The collaboration between these three labs could mean relief to many of those suffering from a variety of diseases.
“To have spent decades on this research and have such promising results is truly exhilarating,” Singh said. “At the end of the day, what matters most is improving health outcomes for our patients. This work represents a very important step towards developing a new approach to treat the most difficult of cancers and hopefully increase cure rates.”
The Latest on: Block cancer
- Lancor Scientific Links Use of a Digital Token to Global Blockchain-based Cancer Screening Registry on December 13, 2018 at 7:03 am
Lancor Scientific, an early detection cancer screening start-up, has validated an integrated cancer screening system that will provide users with a seamless journey, using its digital token. London-ba... […]
- Blockchain cancer screening technology developed by tech entrepreneurs in London on December 13, 2018 at 5:38 am
A start-up in London has created a blockchain-based cancer screening system that claims to provide results within minutes. Lancor Scientific, founded at the beginning of 2018, has created a 'Medici' t... […]
- University of Akron men’s soccer: Thyroid cancer no stumbling block for sophomore Diogo Pacheco on December 10, 2018 at 9:07 am
SANTA BARBARA, Calif. — His scar is clearly visible, peeking out over the curved neck of his practice jersey. But University of Akron sophomore Diogo Pacheco is not scarred by the cancer that put it t... […]
- Nice Blocks and Starship Foundation raise $10K for young woman with cancer on December 3, 2018 at 1:44 pm
Last summer Nice Blocks and The Starship Foundation set out with a goal to raise funds and awareness for a little known support service for young women receiving treatment for cancer. Ovarian Tissue C... […]
- J&J Falls After Failing to Block Generic Zytiga Cancer Drug on November 21, 2018 at 11:27 am
(Bloomberg) -- Johnson & Johnson fell the most since February after a U.S. appeals court refused to stop generic versions of its prostate-cancer drug Zytiga from entering the market. The decision coul... […]
- A New Drug Discovery May Halt Spread of Brain Cancer: Study on November 20, 2018 at 1:47 am
Scientists have identified a novel drug that could block glioblastoma -- one of the deadliest form of brain cancer -- from spreading. The tissues in our bodies are largely made of fluid. It moves arou... […]
- Researchers discover a novel method to block immunosuppression in cancer on October 26, 2018 at 4:22 am
Belgian research groups from the UCLouvain and WELBIO, VIB and Ghent University, and the biotechnology company argenx elucidated the three-dimensional structure of an assembly of proteins operating on ... […]
- Novel method to block immunosuppression in cancer on October 25, 2018 at 4:14 pm
Scientists have elucidated the three-dimensional structure of an assembly of proteins operating on cells that dampen immune responses. They also discovered how an antibody can block this assembly and ... […]
- AstraZeneca's Lynparza shown to put brakes on ovarian cancer on October 21, 2018 at 8:10 am
MUNICH (Reuters) - An AstraZeneca drug that blocks a cancer cell’s ability to repair its genetic code greatly reduced the risk of ovarian cancer worsening in a phase III trial, underpinning its lead a... […]
- Rock the Block returns to raise funds and ‘Kick Cancer’ on October 20, 2018 at 10:03 pm
Attendees are shown at Rock the Block on Oct. 27, 2017. LMH Health's annual fundraiser benefits the hospital's oncology unit and Catch a Break, LMH Endowment’s fund to assist with the costs of cancer ... […]
via Google News and Bing News