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ETH researchers are studying what happens when cells grow too large and become senescent. The latest findings may improve cancer treatments.
Living things must grow to develop and reproduce. To produce new biomass, cell growth and division must be coordinated.
Cell growth must be regulated with the environment in multicellular organisms like humans to generate functional tissue or organs. So cell growth is carefully regulated and only occurs when growth signals are available.
But cancer cells differ. They grow unregulated, divide repeatedly, and ignore environmental stop signals. An advantage might be a drawback.
Recently published findings in the journal Molecular Cell indicate that unregulated growth is both a strength and a weakness for cancer cells.
One of these experiments was led by ETH Zurich Institute of Biochemistry Professor Gabriel Neurohr. He and his team have studied how cell development affects function for years. Researchers are also studying what occurs when cells grow too large and enter senescence. This condition causes abnormally large cells that cannot divide. They can still influence their environment by releasing signaling substances.
Normal tissue contains senescent cells that contribute to aging. Some chemical substances can promote senescence, which reduces cell division and is the target of some cancer treatments.
Senescent cells’ size may alter their functioning, according to Neurohr’s colleague Sandhya Manohar. She inhibited growth and division of non-cancerous and breast cancer cell lines in her studies.
In her cell cultures using solely division-suppressing drugs, the cells stopped dividing yet grew and went into senescence. They lost the ability to divide permanently. This effect lasted after Manohar stopped the division inhibitors.
Because the larger cells cannot repair genetic damage like double-stranded DNA breaks, they can no longer divide. The breaks always occur spontaneously when a cell replicates its genetic material before dividing.
These cells also fail to activate p53–p21, a signaling pathway needed to coordinate DNA break recovery. Thus, damage is not corrected efficiently. In larger cells, many irreversible DNA breaks accumulate during division, making division impossible.
However, after discontinuing both division- and growth-inhibiting drugs, the cells divided and multiplied normally again. In cancer treatment, this is exactly what you don’t want, the researchers added.
Drugs that hinder growth and division are already used to treat cancer. Based on cell culture data, treating a tumor with division and growth inhibitors at the same time should increase relapse rate. First using a division inhibitor, then a medicine that destroys cell DNA and prevents division makes more sense according to the researchers.
Thus far, ETH researchers have solely examined their new results on cell cultures. The scientists cannot apply these findings to clinical practice since cell growth and division depend on the cell environment. Thus, organoids or tissue samples must be tested initially to evaluate the treatment. Division inhibitor and other drug combinations are being studied in clinical trials.
Studies by three additional international research teams in the same issue of Molecular Cell endorse Neurohr’s ETH team’s theory.
These findings reveal that division inhibitors work on hyperactive cancer cells. The findings may affect cancer treatment in the long run because these compounds are already used to treat some breast cancers.
Sources:
Sandhya Manohar et al. (2023). Genome homeostasis defects drive enlarged cells into senescence, Molecular Cell. DOI: 10.1016/j.molcel.2023.10.018
https://phys.org/news/2023-11-growth-weakness-cancer-cells.html
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