How chemotherapy alters DNA of cancer cells and may influence treatment resistance

What is it about?

Chemotherapy is a powerful tool for killing cancer cells, but it can also cause unintended genetic changes in the cells that survive. These changes might make the cancer harder to treat in the future or even lead to new tumors. Our study focused on how a common chemotherapy drug, doxorubicin, affects the DNA of breast cancer cells. Using state-of-the-art techniques, including organoid culture and single-cell sequencing, we discovered that doxorubicin causes major DNA rearrangements and instability in some surviving cells. Our single-cell multi-omics approach allowed us to measure the frequency of these genetic rearrangements in three different cell types—basal, luminal progenitor, and mature luminal—revealing their uniform susceptibility to genetic instability. This means that while the drug is effective in killing cancer, it may also leave behind cells with unpredictable genetic changes, creating conditions that allow cancer to evolve and resist treatment.

Featured Image

Photo by Louis Reed on Unsplash

Photo by Louis Reed on Unsplash

Why is it important?

Since chemotherapy is widely used to treat various types of cancer, it is crucial to understand its unintended effects. By identifying how the chemotherapy drug doxorubicin reshapes cancer cell DNA, our study highlights the need for strategies to minimize these harmful changes. Understanding these risks could lead to improved treatments that are both more effective and safer for patients in the long run.

Perspectives

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Each of us knows someone who has battled cancer, whether as a patient, colleague, or family member. Naturally, we all want treatments that are both effective and cause minimal harm. However, our study reveals that while some drugs, like doxorubicin, may work well in the short term, they can also promote cancer resistance in ways we cannot fully predict yet. For me, this study highlights the critical importance of basic science – only by understanding the hidden effects of treatment can we develop new therapies that are more effective and safer.

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