Small stress proteins, biomarkers of cancer

Abstract

Many oncogenic agents/events generate in cancer cells stress-responsive proteins, also known as heat shock proteins (HSPs). These proteins are implicated in the genesis as well as in the progression of cancer; the small HSPs share the chaperone activity of the other HSPs and thus the small HSPs should also be described as chaperones of tumorigenesis. Since the small HSPs are found at relatively high levels in tumor cells, the study of the expression of these proteins is of high interest as biomarkers of cancer. In this chapter we have analysed the evidence regarding its usefulness: 1) to detect in fluids and tissues the early changes in cell transformation, 2) to help in the diagnosis of the disease, 3) in predicting the recurrence, aggressiveness and the development of metastasis, and 4) to predict the response to therapies and to monitor the efficacy/safety of therapeutic agents. In breast cancer, earlier studies and more recent proteomic studies reveal that the small HSPs are mainly implicated in the response to therapies, HSPB1 (HSP27) appears as a biomarker of resistance to different anticancer therapies. In other tumors, like in prostate cancer, they appear as biomarkers of disease prognosis, while in uterine cervical cancer HSPB1 appears as a marker of cell differentiation. The molecular pathways implicated in the small HSPs activation and the association of these proteins with other proteins result in a unique molecular context in each cancer cell type and ultimately in each patient appearing as biomarkers of different situations. Overall, it is evident that more studies on the topic of biomarkers of anticancer therapies are needed to change the way we treat cancer patients, but so far it seems that the small HSPs, in conjunction with other biomarkers, have a great future to achieve tailored-treatment strategies.