Background: Inherent or acquired chemo resistance in cancer patients has been a perpetual
limitation in cancer treatment. Expanding knowledge on essential cellular processes opens a new
window for therapeutic targeting. Ribosome biogenesis is a process that shows potential due to its
fundamental role in cell development and contribution to tumorigenesis as a result of its upregulation.
Inhibiting components of ribosome biogenesis has been explored and has shown interesting
results. Yet, an important key component, methyltransferase Fibrillarin (FBL), which influences
both the abundance and composition of ribosomes, has not been exploited thus far.
Methods: In this literature review, we describe relevant aspects of ribosome biogenesis in cancer to
emphasize the potential of FBL as a therapeutic target, in order to lower the genotoxic effects of
Results: Remarkably, the amplification of the 19q13 cytogenetic band, including the gene coding
for FBL, correlated to cell viability and resistance in pancreatic cells as well as to a trend toward a
shorter survival in pancreatic cancer patients.
Targeting ribosome biogenesis, more specifically compared to the secondary effects of chemotherapeutics
such as 5-fluorouracil or oxaliplatin, has been achieved by compound CX-5461. The cell
dependent activity of this Pol I inhibitor has been reported in ovarian cancer, melanoma and leukemia
models with active or mutated p53 status, presenting a promising mechanism to evade p53 resistance.
Conclusion: Targeting critical ribosome biogenesis components in order to decrease the genotoxic
activity in cancer cell looks promising. Hence, we believe that targeting key protein rRNA methyltransferase
FBL shows great potential, due to its pivotal role in ribosome biogenesis, its correlation
to an improved survival rate at low expression in breast cancer patients and its association with p53.