RB1 and cancer: ,22 On the other hand, oncogenic mutations in downstream pathway genes are associated with decreased dependencies on upstream genes of the same pathway; e.g., cell lines with inactivating mutations in RB1 show decreased dependency on CDK6. These results show the importance of considering pathway topology in the design of cancer therapeutic strategies; for example, a current strategy for treating tumors with activating mutations in undruggable oncogenes is to inactivate downstream genes.105