Targeting the Arachidonic Acid Cascade in Cancer: Recent Advances in Enzyme Inhibitor Design

Cancer is a multifactorial disease involving multiple interrelated molecular targets and signaling pathways. Some epidemiological studies have suggested that nonsteroidal anti-inflammatory drugs could reduce the incidence of certain types of cancer, indicating the interplay between inflammation and cancer. Designing compounds that inhibit an enzyme of the arachidonic acid inflammatory cascade while exhibiting anticancer effects has emerged as a promising strategy.

A descriptive review and analysis of recently published studies on the synthesis of compounds that target two enzymes of the arachidonic acid cascade and simultaneously exhibit anticancer activity was performed.

Numerous cyclooxygenase-2 (COX-2) inhibitors with anticancer activity are known. Fewer examples exist for 5-lipoxygenase (5-LOX) inhibitors, while many dual COX-2/5-LOX inhibitors also display anticancer effects. Some examples of dual inhibitors with anticancer potential include 5-LOX/microsomal prostaglandin E2 synthase (mPGES), and COX-2/soluble epoxide hydrolase inhibitors. There are also compounds designed to inhibit three targets: COX-2, 15-LOX, and carbonic anhydrase.

Given the complex interplay between inflammation and cancer, the term "anticancer effects" encompasses various therapeutic opportunities, ranging from adjuvant therapy and chemoprevention to angiogenic and cytotoxic activity.

This multitarget approach highlights the broad therapeutic possibilities of targeting inflammatory pathways, establishing a direction for the development of innovative anticancer therapies with improved safety profiles.