Abstract
Lysophosphatidic acid (LPA) and its receptors, LPA1–6, are integral parts of signaling pathways involved in cellular proliferation, migration and survival. These signaling pathways are of therapeutic interest for the treatment of multiple types of cancer and to reduce cancer metastasis and side effects. Validated therapeutic potential of key receptors, as well as recent structure–activity relationships yielding compounds with low nanomolar potencies are exciting recent advances in the field. Some compounds have proven efficacious in vivo against tumor proliferation and metastasis, bone cancer pain and the pulmonary fibrosis that can result as a side effect of pulmonary cancer radiation treatment. However, recent studies have identified that LPA contributes through multiple pathways to the development of chemotherapeutic resistance suggesting new applications for LPA antagonists in cancer treatment. This review summarizes the roles of LPA signaling in cancer pathophysiology and recent progress in the design and evaluation of LPA agonists and antagonists.
Financial & competing interests disclosure
The author has 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.
No writing assistance was utilized in the production of this manuscript.