Secreted protein acidic and rich in cysteine (SPARC) (SPARC)

Secreted protein acidic and rich in cysteine (SPARC), also known as osteonectin, is a matricellular glycoprotein primarily involved in the regulation of cell-matrix interactions and extracellular matrix (ECM) remodeling (UniProt P09486). It is highly expressed during development and tissue repair, but in adults, its expression is often restricted to areas of high ECM turnover, such as the stroma of various solid tumors (PubMed: 24419447). In the context of cancer, SPARC is frequently overexpressed by tumor-associated fibroblasts and has been implicated in promoting tumor invasion, metastasis, and angiogenesis (PubMed: 18337440). A key pharmacological interest in SPARC stems from its high affinity for albumin, which led to the hypothesis that it facilitates the delivery of nab-paclitaxel, an albumin-bound nanoparticle formulation of paclitaxel, to the tumor microenvironment (PubMed: 25538256). By binding the albumin component of the drug, SPARC was thought to act as a "sink," increasing the local concentration of the chemotherapeutic agent within the stroma (PubMed: 24419447). However, clinical studies, including retrospective analyses of the MPACT trial in pancreatic cancer, have yielded conflicting results regarding the correlation between SPARC expression and patient response to nab-paclitaxel (PubMed: 27126254). Despite these controversies, SPARC remains a significant target of interest for understanding drug delivery mechanisms and the role of the tumor microenvironment in chemoresistance.

Other names

OsteonectinONBM-40Basement-membrane protein 40

SPARC binds to the albumin component of nab-paclitaxel, potentially sequestering the drug within the tumor stroma and increasing its local concentration.