Question ID: WS-106
Submitted by: Lauren Merlo
July 6, 2011
How do cancer cells to survive/proliferate despite unstable genomes and high mutational loads? What does this tell us about the difference in distribution of selectively advantageous mutations in cancer compared to other systems and the proportion of cancer cell divisions that can produce viable cells? Finally, what is the relationship between cancer mutation rate and cancer progression, and can this be harnessed as either a biomarker of progression or as a target for cancer therapy?
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Comments
Submitted By Hearn Cho
This is an important question - many cancers such as multiple myeloma are characterized by genomic instability, with new cytogenetic abnormalities, deletions or mutations, and other genetic changes detected as disease progresses. These contribute to "clonal evolution" of more malignant disease, but also implies that the tumor cells circumvent DNA damage/repair pathways that mediate apoptosis in normal cells. Tumor cell survival cannot be explained by deletions or mutations of well-characterized tumor suppressors, such as p53, alone. There may be previously unappreciated mechanisms used by tumor cells to inhibit pro-apoptotic DNA repair pathways that may be valuable therapeutic targets.
