Chapters authored
Extracellular Matrix in Tumor Angiogenesis
Extracellular matrix (ECM) is a complex three-dimensional network that provides structure, strength, and contextual information for cellular growth, communication, differentiation, survival, adhesion, and migration. ECM basic proteins resist compressive forces and/or allow rapid diffusion, others strengthen the matrix, and give resilience or modulate cell-matrix interactions. ECM undergoes turnover and remodeling physiologically and during inflammation, wound repair and tumor invasion. Remodeling of the ECM is an integral component of the angiogenic process and depends on the composition of matrix molecules, soluble pro-angiogenic and anti-angiogenic factors, and their spatial regulation. This review will focus on the myriad roles of those molecules and will emphasize their involvement in critical points of angiogenesis.
Part of the book: Tumor Angiogenesis and Modulators
BRCA Gene Mutations and Prostate Cancer
Prostate cancer remains the second most common cancer in men, with diverse courses from indolent cases to aggressive diseases. Among the key factors implicated in its pathogenesis are genomic alterations such as the TMPRSS2-ERG and related fusion oncogenes, loss of tumor suppressor PTEN, p53 or NKX3.1, inflammation, enhanced DNA damage, and chromosomal instability. Men with prostate cancer who carry BRCA1/2 mutations are at more risk of worse disease and poor prognosis. Cancer cells with mutant BRCA1 or BRCA2 repair genes with defects in homologous recombination are vulnerable to PARP inhibitors that target the genetic phenomenon known as synthetic lethality to exploit faulty DNA repair mechanisms. With relevance to prostate cancer, other features of cancer cells may also sensitize to PARP inhibitors, including aberrant transcription due to the androgen-driven fusion oncogene TMPRSS2-ERG or PTEN loss. Several models of synthetic lethality and potential biomarkers suggested up to date are also discussed. The chapter also highlights the importance of genetic screening of men with BRCA and shows diagnostic utility of plasma-derived circulating tumor DNA.
Part of the book: BRCA1 and BRCA2 Mutations