Nano albumin bound-paclitaxel in pancreatic cancer: Current evidences and future directions

Abstract

Pancreatic cancer (PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound (Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phase III study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials.

Metabolism of pancreatic cancer: paving the way to better anticancer strategies

“…3). Nano albumin-bound (nab) paclitaxel delivers a high concentration of paclitaxel within pancreatic tumors, resulting in the inhibition of microtubule depolymerization and cancer cell division [134,135]. Benefiting from the synergistic effects [136,137], the clinical application of nab paclitaxel often occurs in combination with gemcitabine.…”

Differential Dependency of Human Pancreatic Cancer Cells on Targeting PTEN via PLK 1 Expression

“…Of interest, a blockade of PTEN has shown a critical rationale beyond other anti-pancreatic cancer strategies. Treatment with chemotherapeutics such as gemcitabine, FOLFIRINOX, and nanoparticle albumin-bound paclitaxel (nAb-PTX) have been reported to induce severe side effects including anemia, depilation, diarrhea, and vomiting in almost all patients [22][23][24][25][26][27][28][29]. In our study, we demonstrated that targeting PTEN had no basal cytotoxicity on the human pancreatic duct epithelial cell line H6c7, which induced the viability and migration features of H6c7 cells.…”

A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/− nab-paclitaxel in elderly pancreatic cancer patients (GrantPax)

“…However, a CGA or a stratification of the patients by functional status is not included in this trial. Regarding Gem/NabP combination therapy, a retrospective analysis suggested that the combination was effective in elderly patients and exhibited a different, but tolerable toxicity profile [ 32 , 33 ]. GrantPax prospectively evaluates this combination in elderly patients using CGA to stratify patients based on functional status.…”