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
- Common arthritis drugs could block spread of breast cancer, study suggestson November 19, 2019 at 7:49 pm
Simple arthritis drugs used on the NHS could help stop breast cancer spreading, research suggests. Scientists propose that arthritis drugs anakinra, canakinumab and sulfasalazine could be re-purposed ...
- Arthritis drugs prescribed on the NHS could slash the risk of breast cancer spreading to boneson November 19, 2019 at 4:02 pm
They hope the pills - anakinra, brand name Kineret, canakinumab (Ilaris), and sulfasalazine (Azulfidine) - could be re-purposed for cancer patients in the future. All three drugs block a protein ...
- Arthritis drugs could prevent fatal spread of breast canceron November 19, 2019 at 4:01 pm
Arthritis drugs used on the NHS could prevent the fatal spread of breast cancer, research suggests. Scientists believe the common medications could be re-purposed to help block cancer reaching bones.
- Chemotherapy impacts on the cellular response to CDK4/6 inhibition: distinct mechanisms of interaction and efficacy in models of pancreatic canceron November 19, 2019 at 12:08 pm
Gemcitabine largely ablates the function of CDK4/6 inhibition in S-phase arrested cells when administered contemporaneously; although, when cells recover from S-phase block they exhibit sensitivity to ...
- Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathwayon November 19, 2019 at 8:35 am
Fig. 3: Upregulation of PTP1B promotes proliferation and migration of pancreatic cancer cells. Fig. 4: Inhibition of PTP1B activity by small-molecule inhibitor blocks PDAC cell proliferation and ...
- Leukemia-SIK3 Blocks (image)on November 19, 2019 at 8:18 am
Bioluminescence imaging of mice whose cancer cells were tagged with a firefly-derived enzyme shows how the drug YKL-05-099 blocks the SIK3 pathway to slow the progression of leukemia. Disclaimer: AAAS ...
- Michigan Lawmakers Overturn a Bad Regulation Restricting Access to Cancer Treatmentson November 18, 2019 at 3:45 pm
The American Cancer Society warned that the new regulations meant some patients "may not be ... A 2002 reform to the state's Certificate of Need laws let them block the regulations from taking effect.
- New insight into a cancer-shielding protein could guide a new generation of cancer treatmentson November 18, 2019 at 4:29 am
"These proteins keep our immune systems from finding and destroying the cancer cells," Mehta says. "Until now, researchers didn't have a detailed picture of what VISTA looks like on a molecular level.
- Gloucester couple both diagnosed with lung cancer 5 weeks aparton November 18, 2019 at 2:35 am
During Lung Cancer Awareness Month, they have a story to share and a reminder for others ... According to a release, Virginia State Police say the crash occurred in the 4000 block of Hickory Fork Road ...
- Researchers block metastasis-promoting enzyme, halt spread of breast canceron November 14, 2019 at 8:10 am
In a breakthrough with important implications for the future of immunotherapy for breast cancer, UC San Francisco scientists have found that blocking the activity of a single enzyme can prevent a ...
via Google News and Bing News