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In a groundbreaking study published in the Proceedings of the National Academy of Sciences, researchers from the University of North Carolina at Chapel Hill have revealed how cancer cells manage to evade drug treatments. This discovery could pave the way for new therapeutic strategies to combat cancer.
Cancer cells are notorious for their ability to proliferate rapidly, a process driven by their manipulation of cell cycles. Anti-cancer drugs aim to halt this uncontrolled growth by triggering a complex sequence of genetic and cellular events. However, these treatments often yield inconsistent results, with cancer cells frequently finding ways to survive and continue growing.
The research team, led by Jean Cook from the Department of Biochemistry and Biophysics, identified a critical enzyme that plays a key role in stopping cancer cell proliferation, particularly during treatment with anti-cancer drugs. This enzyme’s function varies among individuals, contributing to the mixed efficacy of cancer therapies.
The study highlighted that cells regulate protein expression by turning genes “on” and “off.” Certain proteins ensure precise and effective cell division, akin to musicians in an orchestra guided by a conductor. However, cancer cells can deactivate these regulatory proteins, allowing uncontrolled division and DNA replication.
To explore the role of protein degradation in halting cell growth, Cook and graduate student Brandon Mouery treated cultured human cells with palbociclib, a drug used to treat metastatic breast cancer. Using advanced techniques such as microscopy, flow cytometry, and proteomics, they discovered that the enzyme APC/C (Anaphase Promoting Complex/Cyclosome), which targets proteins for degradation to regulate the cell cycle, enhances the effectiveness of palbociclib.
This finding suggests that APC/C levels in tumors could help predict patient responses to palbociclib and similar drugs. Reduced APC/C activity might indicate a poor treatment response or a higher risk of relapse.
Moreover, the researchers observed that both cancerous and non-cancerous cells can bypass drug-induced proliferation arrest. These “escapee” cells struggle to replicate DNA independently and likely delegate DNA replication to proteins that initiate cell division later in the cell cycle. This indicates that cells can use alternate pathways for uncontrolled growth.
“Cell proliferation has been intensively studied for decades, yet we can still be surprised,” Cook noted. “Sometimes our textbook understanding is still quite incomplete, so we need to keep an open mind and continually challenge paradigms.”
These findings could lead to new interventions that induce long-lasting proliferation arrest by exploiting the escape mechanisms and cancer-associated DNA replication errors, potentially forcing cancer cells into a “self-destructive” growth mode.
The study opens new avenues for cancer treatment by highlighting the importance of understanding cellular processes and protein regulation. With continued research, these insights could significantly improve the efficacy of cancer therapies and provide hope for patients worldwide.
