Treatment Strategy Using mtor Pathway in Incurable Prostate Cancer

초록

In spite of androgen deprivation therapy and novel hormone therapy such as enzalutamide or abiraterone has possibility of various regimens, there is still barrier to expect a complete response (CR) in castrate-resistant prostate cancer (CRPC) patients. In these cases, a new strategy using drugs targeting PI3K/AKT/mTOR pathway is necessary. In conclusion, drugs or biomarkers targeting PI3K/AKT/mTOR pathway in patients with CRPC may be used to establish a novel treatment strategy. Patients with prostate cancer are generally known to have a good prognosis; however, it is highly dependent on the risk group. Although the introduction of androgen deprivation therapy and the development of new hormone therapy drugs such as enzalutamide or abiraterone has made various treatment regimens possible, it is still difficult to expect a complete response (CR) in castrate-resistant prostate cancer (CRPC) patients. Despite of cabazitaxel development, patients who are unresponsive to docetaxel and cabazitaxel are classified as patients with incurable prostate cancer. To treat this incurable cancer, drugs with different mechanism of actions are considered. Recently, PARP inhibitors which target glutamine metabolism, a key source of carbon, are anticipated to be introduced in the clinical practice. Nevertheless, treatment strategies incorporating drugs other than PARP inhibitors are needed to treat incurable prostate cancer. As such, a strategic development of drugs targeting PI3K/AKT/mTOR pathway is necessary. The mammalian target of rapamycin (mTOR) is expressed in the representative prostate cancer cell lines such as DU145, PC3, LNCaP, and 22RV1 (Figure 1). According to a review article published in 2016, Park and his colleagues found that mTOR inhibitors have limited effect on prostate cancer. However, studies published afterwards have provided a different point of view.