Does the molecular classification of breast cancer point the way for biomarker identification in prostate cancer?

There is significant variation in clinical outcome between patients diagnosed with prostate cancer(Ca P). Although useful, statistical nomograms and risk stratification tools alone do not always accurately predict an individual's need for and response to treatment. The factors that determine this variation are not fully elucidated. In particular, cellular response to androgen ablation and subsequent paracrine/autocrine adaptation is poorly understood and despite best therapies, median survival in castrate resistant patients is only approximately 35 mo. We propose that one way of understanding this is to look for correlates in other comparable malignancies, such as breast cancer, where markers of at least 4 distinct gene clusters coding for 4 different phenotypic subtypes have been identified. These subtypes have been shown to demonstrate prognostic significance and successfully guide appropriate treatment regimens. In this paper we assess and review the evidence demonstrating parallels in the biology and treatment approach between breast and Ca P, and consider the feasibility of patients with Ca P being stratified into different molecular classes that could be used to complement prostate specific antigen and histological grading for clinical decision making. We show that there are significant correlations between the molecular classification of breast and Ca P and explain how techniques used successfully to predict response to treatment in breast cancer can be applied to the prostate. Molecular phenotyping is possible in Ca P and identification of distinct subtypes may allow personalised risk stratification way beyond that currently available.

Alpha1B adrenoceptor expression is a marker of reduced survival and increased tumor recurrence in patients with endometrioid ovarian cancer

AIM: To investigate the expression patterns of different adrenoceptor isoforms in ovarian cancer and their association with survival and tumor recurrence. METHODS: The protein expression levels of a1 B, a2 C and b2 adrenoceptor were assessed in unselected ovarian cancer using immunohistochemistry on microarrayed archival tissue samples. A database containing clinical and pathology parameters and follow-up was usedto investigate the association between adrenoceptor isoform expression with ovarian specific survival and tumor recurrence, using univariate and multivariate statistical analysis. RESULTS: Expression of a1 B showed an association with reduced ovarian specific survival(P = 0.05; CI: 1.00-1.49) and increased tumor recurrence(P = 0.021, CI: 1.04-1.69) in the whole patient group. On subanalysis the expression of a1 B in endometrioid cancers(χ2 = 5.867, P = 0.015) was found to predict reduced ovarian specific survival and increased tumor recurrence independently of tumor grade, clinical stage and chemotherapy. An association with clinical outcome was not seen for a2 C or b2 AR.CONCLUSION: Alpha1 B adrenoceptor protein was found to predict increased risk of tumor recurrence and reduced mortality in patients with endometrioid type ovarian cancer and should be investigated as a biomarker for identifying patients at increased risk of disease progression. Furthermore, a adrenergic receptor antagonists with a1 B selectivity should be investigated as a possible adjuvant therapy for treating patients with endometrioid cancer. Proof of principle could be tested in a retrospective population study.

Targeting cellular pathways in glioblastoma multiforme

Glioblastoma multiforme(GBM)is a debilitating disease that is associated with poor prognosis,short median patient survival and a very limited response to therapies.GBM has a very complex pathogenesis that involves mutations and alterations of several key cellular pathways that are involved in cell proliferation,survival,migration and angiogenesis.Therefore,efforts that are directed toward better understanding of GBM pathogenesis are essential to the development of efficient therapies that provide hope and extent patient survival.In this review,we outline the alterations commonly associated with GBM pathogenesis and summarize therapeutic strategies that are aimed at targeting aberrant cellular pathways in GBM.