The effective and efficient management of cancer patients relies upon early diagnosis and/or the monitoring of treatment, something that is often difficult to achieve using standard tissue biopsy techniques. Biological fluids such as blood hold great possibilities as a source of non-invasive cancer biomarkers that can act as surrogate markers to biopsy-based sampling. The non-invasive nature of these “liquid biopsies” ultimately means that cancer detection may be earlier and that the ability to monitor disease progression and/or treatment response represents a paradigm shift in the treatment of cancer patients. Below, we review one of the most promising classes of circulating cancer biomarkers: microRNAs (miRNAs). In particular, we will consider their history, the controversy surrounding their origin and biology, and, most importantly, the hurdles that remain to be overcome if they are really to become part of future clinical practice.

GPR55 is an orphan G protein-coupled receptor that may be engaged by some lipid ligands such as lysophosphatidylinositol and cannabinoid-type compounds. Very little is known about its expression pattern and physio-pathological relevance, and its pharmacology and signaling are still rather controversial. Here we analyzed the expression and function of GPR55 in cancer cells. Our data show that GPR55 expression in human tumors from different origins correlates with their aggressiveness. Moreover, GPR55 promotes cancer cell proliferation, both in cell cultures and in xenografted mice, through the overactivation of the extracellular signal-regulated kinase cascade. These findings reveal the importance of GPR55 in human cancer, and suggest that it could constitute a new biomarker and therapeutic target in oncology.

It has been proposed that cannabinoids are involved in the control of cell fate. Thus, these compounds can modulate proliferation, differentiation, and survival in different manners depending on the cell type and its physiopathologic context. However, little is known about the effect of cannabinoids on the cell cycle, the main process controlling cell fate. Here, we show that # 9 -tetrahydrocannabinol (THC), through activation of CB 2 cannabinoid receptors, reduces human breast cancer cell proliferation by blocking the progression of the cell cycle and by inducing apoptosis. In particular, THC arrests cells in G 2 -M via down-regulation of Cdc2, as suggested by the decreased sensitivity to THC acquired by Cdc2-overexpressing cells. Of interest, the proliferation pattern of normal human mammary epithelial cells was much less affected by THC. We also analyzed by realtime quantitative PCR the expression of CB 1 and CB 2 cannabinoid receptors in a series of human breast tumor and nontumor samples. We found a correlation between CB 2 expression and histologic grade of the tumors. There was also an association between CB 2 expression and other markers of prognostic and predictive value, such as estrogen receptor, progesterone receptor, and ERBB2/HER-2 oncogene. Importantly, no significant CB 2 expression was detected in nontumor breast tissue. Taken together, these data might set the bases for a cannabinoid therapy for the management of breast cancer. (Cancer Res 2006; 66(13): 6615-21)