PHARMACOTHERAPY

Attacking the androgen receptor pathway in prostate cancer

Summary

Since the 1940’s the androgen receptor has been the main target for systemic therapy in prostate cancer. Classic hormonal therapy aims at lowering serum testosterone levels or block the androgen receptor ligand-binding domain. Despite disease progression, castration-resistant prostate cancer remains predominantly androgen-driven as novel secondary hormonal therapy with abiraterone acetate or enzalutamide has demonstrated increased overall survival. Promising androgen synthesis inhibitors (orteronel, galeterone), androgen receptor inhibitors (ARN-509, EPI-001, AZD3514) and heat-shock protein modulators are under investigation. Given the upcoming arsenal of systemic therapies and the molecular heterogeneity of castration-resistant prostate cancer, patient-tailored therapy strategies are being explored.

(BELG J MED ONCOL 2013;7(3):111–8)

Statins and cancer

Summary

Although proliferating malignant cells consume cholesterol, this may not completely explain the observed inverse relation between plasma cholesterol levels and the incidence of cancer. Results of studies and meta-analysis, investigating possible adverse effects of cholesterol-lowering therapy did not disclose any consistent promoting or preventive activity of statins on the incidence of frequently occurring cancers. However, statin use may reduce the rate of dedifferentiation and recurrence of established prostate and breast cancer. Furthermore, lipoprotein (-like) ligands for low- and high density lipoprotein receptors on tumour cells can serve as carriers for targeted anti-cancer therapies.

(BELG J MED ONCOL 2013:7(2):46–49)

Targeted therapies in melanoma

The incidence of melanoma has increased continuously these last decades. Fortunately, cure is possible in most cases thanks to diagnosis at an early stage. Nevertheless, in some instances, melanoma is diagnosed at later stages and in other cases relapses occur. Moreover, melanoma is the deadliest cutaneous cancer and more importantly the most common origin of death due to cancer in young people. Thankfully though, hope for these patients has been increasing during the past three decades with the increased insight in the underlying oncogenic mutations. This progress has opened up new perspectives for etiological targeted therapies. This review will focus on the recent advances in melanoma treatment. (BELG J MED ONCOL 2012;6:194–200)

The RANK ligand inhibitor denosumab as novel therapeutic agent in the spectrum of cancer bone disease

Recently, the monoclonal antibody denosumab has been registered as a new first-in-class treatment option for the prevention of skeletal-related events (SREs) in patients with bone metastases from a solid tumour, for the treatment of treatment-induced bone loss (TIBL) in prostate cancer, and the treatment of post-menopausal osteoporosis. The present article reviews the mechanism of action of denosumab and the research leading to the registered indications in cancer patients. (BELG J MED ONCOL 2012;6:118–123)

Tumour markers in metastatic colorectal cancer: clinical implications for treatment with targeted therapy

Targeted therapy with bevacuzimab, cetuximab and panitumumab has expanded the treatment options in metastatic colorectal cancer. Predictive tumour markers for treatment with targeted therapy that have been suggested are Epithelial Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR) expression, KRAS mutation and BRAF mutation status, loss of PTEN and PIK3CA mutation status. Of these, only KRAS has made it into clinical practice. KRAS mutation is a negative predictor for response to cetuximab EGFR inhibitors. No predictive tumour marker for bevacizumab has been identified. In this review, the current evidence on KRAS, BRAF, PTEN, PIK3CA, EGFR and VEGFR expression as predictive tumour markers for targeted therapy is reviewed. (BELG J MED ONCOL 2012;6:52–57)