IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential.

Diabetes in patients with HIV: patient characteristics, management and screening.

BACKGROUND: As HIV management has become more successful during the past years, non-communicable diseases have become more prevalent among HIV-infected individuals. As a result, more HIV-infected patients die of cardiovascular diseases, with diabetes being one of the main risk factors. This study evaluates screening and management of diabetes among HIV-infected patients in a university hospital in the Netherlands. METHODS: We examined clinical characteristics, glycaemic control and cardiovascular risk management of HIV-infected patients with coexisting diabetes, and determined the frequency of diabetes screening in those without. RESULTS: Of 518 HIV-infected patients, 28 had been diagnosed with diabetes (5.4%), mostly (20÷28) after being diagnosed with HIV. Patients with coexisting diabetes were older, had a longer duration of HIV, lower CD4 cell counts and higher body mass index (BMI), and were more likely to use aspirin, statins and antihypertensive medication than those without diabetes (all p < 0.05). HbA1c values were below 7% (53 mmol÷mol) in 54% of patients. Targets for systolic blood pressure (< 140 mmHg), LDL cholesterol (< 2.5 mmol÷l) and BMI (< 25 kg÷m2) were achieved by 82%, 50% and 29% of patients, respectively. Annual ophthalmology examination, screening for microalbuminuria and foot control were rarely performed. Among the patients without known diabetes, diabetes screening during the past year had been performed using (non-fasting) plasma glucose in 56% and HbA1c in 10%, but 42% of patients had not been screened. CONCLUSION: For HIV-infected individuals with diabetes, glycaemic control and cardiovascular risk management were reasonable, but screening for microvascular complications was rarely performed. Annual diabetes screening of HIV-infected patients was not routine.