IGF-R; a new target for prostate cancer treatment?

This review explored the use of insulin-like growth factor receptor blockers as treatment for castration-resistant prostate cancer.

Prostate cancer is dependent on androgens, male hormones such as testosterone, for growth. Therefore androgen deprivation therapy, which blocks the production or action of testosterone needed for tumor growth, is the standard of care in the treatment of prostate cancer. Eventually, however, the cancer becomes resistant to androgen deprivation, referred to as castration-resistant prostate cancer.

In order to further extend survival despite resistance to treatment, research is currently focused at alternative pathways through which to inhibit cancer growth. The insulin-like growth factor type 1 receptor (IGF-1R) is a structure found on many cell types throughout the body, and is an important mediator of cell growth and proliferation. However, the association between IGF-1R levels and cancer severity or aggressiveness has yet been thoroughly investigated. The IGF-1R does however offer a potential therapeutic target for castration resistant prostate cancer. It is hypothesized that targeted therapies blocking the action of IGF-1R could inhibit cancer growth, prevent metastasis and possibly extend patient survival. The current review examined evidence regarding the use of targeted IGF-1R therapies in the treatment of prostate cancer.

Cixutumumab is a recently developed IGF-1R blocker that has been demonstrated to inhibit prostate cancer cell growth in pre-clinical trials. Cixutumumab was also shown to enhance the effectivity of certain chemotherapies, such as docetaxel, in non-human lab studies. In a small phase-II human study including patients with metastatic castration-resistant prostate cancer, 29% of patients treated with cixutumumab experienced an arrest in cancer progression, without signs of growth or further metastasis, for more than 6 months. Currently, several ongoing clinical trials are examining the use of cixutumumab in combination with other cancer therapies (such as chemotherapy or immunotherapies).

Figitumumab, another recently developed IGF-1R inhibitor, was evaluated in a small study including 14 metastatic prostate cancer patients. Figitumumab led to a significant reduction in PSA levels (prostate-specific antigen; a protein produced by prostate cells whose levels rise with growing prostate cancer) in 94% of patients treated. 31% of patients treated experienced a reduction of 50% or greater in PSA levels compared to baseline measurements taken before treatment initiation.

This review concluded that insulin-like growth factor receptor targeting therapies exhibit great potential as treatment for castration-resistant prostate cancer.

Results of large-scale, randomized controlled studies are awaited to confirm the potential benefit and safety of IGF-1R targeting drugs.