Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)
Cancer biomarkers mainly exist as measurable indicators of a carcinogenic process or of a pharmacologic response to a therapeutic maneuver. They are either produced by tumor cells themselves or by the body in response to cancer. Cancer biomarkers, therefore, may be measured not only in tumor tissues but also in normal tissue or bodily fluids. In this chapter, we will break down the current status of tumor tissue-derived biomarkers, as well as discuss the emergence of blood- or urine-based biomarkers in renal cell carcinoma (RCC).
Fig 4.1. Biomarker-relevant biologic pathways in renal cell carcinoma (RCC). In VHL-/tumor cells, the absence of pVHL results in the accumulation of hypoxia-inducible factor alpha (HIF-α). HIF accumulation could also be secondary to the activation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. mTOR phosphorylates and activates pS6K, which leads to increasing translation of downstream target proteins, including cyclin D, Myc, and HIF. Activated mTOR also phosphorylates 4E-BP1, disrupts this complex, and allows eIF-4E to stimulate the mRNA translation as well. Activated HIF translocates into the nucleus and results in the transcription of multiple HIFtarget genes, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). These proteins bind to their receptors and cause cell migration, proliferation, and permeability. RCC biomarkers could be derived from cell components of tumor cell itself, including DNA, RNA, protein, and metabolites. The soluble cell components could also migrate from the cell into the blood vessels and be detected in blood and urine of RCC patients
Biomarkers can be defined according to the following categories:
- Early detection biomarkers – used to screen patients for cancer
- Diagnostic biomarkers – used to assess the presence, absence, or type of cancer
- Prognostic biomarkers – used to evaluate different phenotypes that correlate with clinical behaviors and/or survival outcomes
- Predictive biomarkers – used to predict individualized response to therapies, especially targeted therapies
A particular biomarker may satisfy more than one category. For example, a circulating tumor marker may aid in early detection and diagnostic clarification and have prognostic or predictive relevance in the management of cancer.
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