News / Targeting MLL complex in CRPC
Targeting MLL complex in CRPC
4/3/2015
Resistance to androgen deprivation therapies and increased androgen
receptor (AR) activity are major drivers of castration-resistant
prostate cancer (CRPC). Although prior work has focused on targeting AR
directly, co-activators of AR signaling, which may represent new
therapeutic targets, are relatively under-explored. MCTP researchers and colleagues demonstrated
that the mixed-lineage leukemia protein (MLL) complex, a well-known
driver of MLL fusion-positive leukemia, acts as a co-activator of AR
signaling. AR directly interacts with the MLL complex via the menin-MLL
subunit. Menin expression is higher in CRPC than in both hormone-naive
prostate cancer and benign prostate tissue, and high menin expression
correlates with poor overall survival of individuals diagnosed with
prostate cancer. Treatment with a small-molecule inhibitor of menin-MLL
interaction blocked AR signaling and inhibited the growth of
castration-resistant tumors in mice. Taken together, this work
identifies the MLL complex as a crucial co-activator of AR and a
potential therapeutic target in advanced prostate cancer. The results of this study was published in Nature Medicine.
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