Researchers at the Medical University of South Carolina in Charleston have uncovered a groundbreaking discovery that sheds light on why cancer may recur in patients following chemotherapy or radiotherapy. The study, published in the Journal of Biological Chemistry, reveals the role of polyploid giant cancer cells (PGCCs) in cancer recurrence. These oversized cells with multiple nuclei have the ability to adapt and survive post-therapy, leading to tumor regrowth.
The research team, led by Dr. Christina Voelkel-Johnson, found that PGCCs manipulate select genes in prostate cancer cells to protect themselves from therapy-induced stress. These cells later regain their ability to divide, ultimately leading to cancer recurrence. The study challenges previous assumptions about how cancer therapies work and highlights the importance of targeting PGCCs with specific inhibitors, such as p21, during treatment to improve outcomes.
Voelkel-Johnson and her colleagues made this discovery while studying an inhibitor associated with durable cures after radiotherapy. They observed that the inhibitor did not kill cancer cells more effectively but instead prevented the generation of offspring from PGCCs. These findings suggest that blocking the transition of PGCCs back into single-nucleus cancer cells is crucial for preventing tumor relapse.
The team identified key cell-signaling pathways that cancer cells manipulate to become PGCCs in response to therapy stress. One protein of interest was p21, induced by a protein called p53 in normal cells under stress. However, in cancer cells lacking p53, increases in p21 did not prevent the duplication of damaged DNA, leading to the generation of PGCCs.
By blocking increases in p21, the researchers were able to prevent the transformation of stressed cancer cells into PGCCs. This interference also prevented the generation of daughter cells from PGCCs, which are responsible for tumor recurrence in some patients post-therapy. The study provides valuable insights into novel mechanisms that could be targeted to improve patient outcomes after cancer treatment.
Voelkel-Johnson plans to further explore ways to prevent the generation of daughter cells from PGCCs to enhance therapy efficacy. She also aims to investigate the impact of various combination treatment regimens delivered concurrently with cancer therapy on recurrence rates in different types of cancers. The findings offer hope for developing more effective strategies to combat cancer recurrence and improve patient outcomes in the future.