Targeting Phospholipase D with Small-Molecule Inhibitors as a Potential Therapeutic Approach for Cancer Metastasis

Abstract

Phospholipase D (PLD)1 and PLD2, the classic mammalian members of the PLD superfamily, have been linked over the past three decades to immune cell function and to cell biological processes required by cancer cells for metastasis. However, owing to the lack of effective small-molecule inhibitors, it has not been possible to validate these roles for the PLDs and to explore the possible utility of acute and chronic PLD inhibition in vivo. The first such inhibitors have recently been described and demonstrated to block neutrophil chemotaxis and invasion by breast cancer cells in culture, increasing the prospects for a new class of therapeutics for autoimmune disorders and several types of metastatic cancer.

Keywords:

• breast cancer
• FIPI
• halopemide
• inhibitor
• lipid signaling
• neutrophil chemotaxis
• phospholipase D

Financial & competing interests disclosure

Supported by NIH awards GM071520 and GM084251 and the Carol Baldwin Breast Cancer Foundation. The authors have no other 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 apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Supported by NIH awards GM071520 and GM084251 and the Carol Baldwin Breast Cancer Foundation. The authors have no other 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 apart from those disclosed.