title: nab-Paclitaxel mechanisms of action and delivery.
abstract: Taxanes are a key chemotherapy component for several malignancies, including metastatic breast cancer (MBC), ovarian cancer, and advanced non-small cell lung cancer (NSCLC). Despite the clinical benefit achieved with solvent-based (sb) taxanes, these agents can be associated with significant and severe toxicities. Albumin-bound paclitaxel (Abraxane; nab®-Paclitaxel), a novel solvent-free taxane, has demonstrated higher response rates and improved tolerability when compared with solvent-based formulations in patients with advanced MBC and NSCLC. The technology used to create nab-paclitaxel utilizes albumin to deliver paclitaxel, resulting in an advantageous pharmacokinetic (PK) profile. This review discusses the proposed mechanism of delivery of nab-paclitaxel, including an examination into a hypothesized greater ability to leverage albumin-based transport relative to sb-paclitaxel. An advantageous PK profile and the more efficient use of albumin-based transport may contribute to the preclinical finding that nab-paclitaxel achieves a 33% higher tumor uptake relative to sb-paclitaxel. Another possible contributing factor to the tumor accumulation of nab-paclitaxel is the binding of albumin to secreted protein acidic and rich in cysteine (SPARC), although the data supporting this relationship between SPARC and nab-paclitaxel remain largely correlative at this point. Recent data also suggest that nab-paclitaxel may enhance tumor accumulation of gemcitabine in pancreatic cancer treated with both agents. Additionally, a possible mechanistic synergy between nab-paclitaxel and capecitabine has been cited as the rationale to combine the two agents for MBC treatment. Thus, nab-paclitaxel appears to interact with tumors in a number of interesting, but not fully understood, ways. Continued preclinical and clinical research across a range of tumor types is warranted to answer the questions that remain on the mechanisms of delivery and antitumor activity of nab-paclitaxel.
authors.affiliation: Sarah Cannon Research Institute, 250 25th Avenue North, Suite 100, Nashville, TN 37203, USA. dyardley@tnonc.com
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
mesh_terms: D000418:Albumins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel
keywords: Cancer; Mechanism of action; Mechanism of delivery; Taxane; nab-Paclitaxel