Towards individualisation of treatment in endometrial cancer
2012
Endometrial cancer is the most common gynaecological cancer in the Western world, and its incidence is rising in most European countries, largely owing to increasing obesity. The majority are early stage, low-grade tumours associated with a favourable prognosis, and current classifications describe type 1 and 2 categories based primarily on morphological and molecular criteria. Hormone therapy has been shown to be effective predominantly in type 1 tumours and subgroups identified by classical receptor evaluation (Decruze and Green, 2007). Recent clinical interest has focused on identifying poor prognosis tumours and evaluating the benefit of adjuvant cytotoxic chemotherapy. This follows the demonstration of survival gain in advanced disease (Humber et al, 2007), but these therapies are toxic and not suitable for many elderly patients with concurrent medical problems. Activation of the P13K pathway has been observed in ~30% of type 1 endometrial cancers and 20% of type 2 endometrial cancers, although mTOR-directed targeted therapy has shown only modest activity to date. Other PI3K pathway alterations leading to deregulated signalling include PIK3CA amplification or mutation and mutation in the AKT gene (Dedes et al, 2011). These observations provide interesting challenges for a personalised approach to the treatment of these tumours.
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