Editing Castrate-Resistant Prostate Cancer (section)

===== Targeted treatments =====

* Despite negative studies with bevacizumab and aflibercept, angiogenesis remains a valid therapeutic target in prostate cancer, as exemplified by the novel agent tasquinimod.
* Because of the reciprocal interactions between the PI3K/Akt/mTOR pathway and the AR signaling pathway, dual inhibition of both pathways concurrently will likely represent the most fruitful therapeutic strategy
* Cabozantinib
** Inhibitor of c-Met and VEGFR2
** Studied in two phase III trials in men with mCRPC with progressive disease following treatment with docetaxel and a novel AR-directed agent (abiraterone or enzalutamide)
*** COMET-1 evaluated the efficacy of single-agent cabozantinib versus placebo, with a primary end point of overall survival.
*** COMET-2 investigated the effect of cabozantinib versus mitoxantrone on quality-of-life measures and pain control; the primary end point of that study was the frequency of durable pain responses lasting at least 12 weeks (whereas overall survival was a secondary end point).
*** These trials were considered the registrational studies for cabozantinib in advanced CRPC. Both studies failed to meet their primary end points. However, '''cabozantinib appeared particularly active in treating bone metastases''', with 12% of patients showing complete resolution of disease on technetium-99 bone scan. Reductions in pain scores and narcotic use were also observed in a significant proportion of patients. Importantly, PSA changes did not correlate with the favorable results seen on imaging studies or other signs of clinical benefit; some patients exhibited rising PSA levels despite reductions in the size of soft-tissue lesions or bone metastases.
* Custirsen is an antisense oligonucleotide against clustering mRNA, which may play a role in reversing resistance to taxane chemotherapies