Case Western Reserve University researchers have discovered a more effective way to treat cancer by degrading the LSD1 protein, challenging traditional approaches and potentially leading to more effective cancer treatments.
Biochemists at Case Western Reserve University are focusing on the degradation of a key protein that drives cancer; a major shift in research.
This protein is LSD1 (lysine-specific histone demethylase 1A), which acts as a traffic policeman in human cells. It controls gene activity during embryonic development and regulates gene expression throughout life.
In recent years, scientists have also discovered that overexpression of LSD1 - such as producing too much protein - can lead to the development of cancer and heart disease.
Recently, some researchers have hoped to slow cancer growth by blocking LSDI's catalytic activity—LSDI's chemical reaction stimulates cell growth but also appears to cause its overexpression. But Kaixiang Cao, assistant professor of biochemistry, is leading a team that challenges that assumption: School of Medicine researchers believe they may have greater success slowing or stopping cancer growth in stem cells by degrading the entire LSD1 protein, rather than just short-circuiting the chemical reactions that cause its overexpression.
Their research was recently published in the journal Nature Communications.
"We need a really precise and efficient way to target these proteins, and our study showed that stopping catalysis might be effective (blocking overexpression) in 15 percent of cases, whereas our approach is closer to 80 percent," Cao said. "So if we can develop a degrader of LSD1, we can help patients reduce the number of treatments they need - even if we can't completely cure the cancer."
He and his team were surprised that LSD1 acted primarily in a catalysis-independent manner, but now that they have provided the research community with "theoretical basis that this would be a more effective way to treat these diseases," they will begin further testing, first in cancer tissue, then in animal models, and eventually in human trials.
"This is the future - add a degrader and you can completely kill the protein," he said. "This technology already exists because other researchers have worked on other proteins, but not on LSD1."