Adenosine pathway inhibitors: novel investigational agents for the treatment of metastatic breast cancer

ABSTRACT

Introduction

The adenosine pathway has been suggested to play a key role in several carcinogenetic processes, with the metabolism of adenosine-5′-triphosphate (ATP) and its derivatives reported to be dysregulated in breast cancer. Preclinical evidence has supported the role of adenosine in the pathogenesis of this malignancy as well as the development of selective adenosine pathway inhibitors.

Areas covered

The paper overviews the evidence regarding the use of adenosine pathway inhibitors in breast cancer; a literature search was conducted in January 2022 of Pubmed/Medline, Cochrane library, and Scopus databases.

Expert Opinion

The adenosine pathway regulates inflammation, apoptosis, metastasis, and cell proliferation in breast cancer cells, and adenosine pathway inhibitors have yielded encouraging results in early-phase clinical trials. Well-designed, multicenter studies focused on monotherapies and combination therapies (which include immune checkpoint inhibitors) are warranted in this setting.

KEYWORDS:

• Breast cancer
• triple-negative breast cancer
• oleclumab
• CD73
• CD39
• adenosine
• immunotherapy

Article Highlights

• Novel systemic therapies have recently made a breakthrough in breast cancer, as witnessed by the emerging of immune checkpoint inhibitors (ICIs) and small molecules.

• Among investigational agents under exploration, adenosine pathway inhibitors have recently attracted a lot of attention.

• This pathway represents a promising target to enhance anti-tumor immunity, and results from early-phase clinical trials assessing combination treatments including immunotherapy are encouraging.

• Additional translational evidence is required to better select patients that might benefit from this investigational, and yet poorly studied, therapeutic strategy.

Declaration 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 research received no financial support.