Metabolism and structure of PDA as the target for new therapies: possibilities and limitations for nanotechnology

ABSTRACT

Introduction

Certainly, pancreatic ductal adenocarcinoma poses one of the greatest challenges in current oncology. The dense extracellular matrix and low vessel density in PDA tumor impede the effective delivery of drugs, primarily due to the short pharmacokinetics of most drugs and potential electrostatic interactions with stroma components.

Area covered

Owing to the distinctive metabolism of PDA and challenges in accessing nutrients, there is a growing interest in cell metabolism inhibitors as a potential means to inhibit cancer development. However, even if suitable combinations of inhibitors are identified, the question about their administration remains, as the same hindrances that impede effective treatment with conventional drugs will also hinder the delivery of inhibitors. Methos including nanotechnology to increase drugs in PDA penetrations are reviewed and discussed.

Expert opinion

Pancreatic cancer is one of the most difficult tumors to treat due to the small number of blood vessels, high content of extracellular matrix, and specialized resistance mechanisms of tumor cells. One possible method of treating this tumor is the use of metabolic inhibitors in combinations that show synergy. Despite promising results in in vitro tests, their effect is uncertain due to the tumor’s structure. In the case of pancreatic cancer, priming of the tumor tissue is required through the sequential administration of drugs that generate blood vessels, increase blood flow, and enhance vascular permeability and extracellular matrix. The use of drug carriers with a size of 10-30 nm may be crucial in the therapy of this cancer.

KEYWORDS:

• Pancreatic cancer
• Metabolic therapy
• Metabolism inhibitor
• Nanoteraphy
• EPR
• Nanoparticles

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Article highlights

• Pancreatic cancer is one of the greatest challenges in modern oncology

• Disseminated tumor cells reside in isolated niches surrounded by the cellular matrix and other cells that make up the tumor structure

• This complex structure causes resistance cancer cells to drugs but also poor access to nutrients, which may be the Achilles heel of this tumor

• Metabolic inhibitors targeting energy harvesting pathways are probably the best approach to PDA therapy

• To reach cancer with new therapy, it is necessary to develop ways to increase tumor penetration by drugs or nanoparticles

• Currently, most of the data enabling to increase the effectiveness of PDA therapy are available and are gradually improving the treatment of this dangerous tumor

Declarations of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.