The limitations of current chemotherapeutic
drugs are still a major
issue in cancer treatment. Thus, targeted multimodal therapeutic approaches
need to be strategically developed to successfully control tumor growth
and prevent metastatic burden. Inflammation has long been recognized
as a hallmark of cancer and plays a key role in the tumorigenesis
and progression of the disease. Several epidemiological, clinical,
and preclinical studies have shown that traditional nonsteroidal anti-inflammatory
drugs (NSAIDs) exhibit anticancer activities. This Perspective reports
the most recent outcomes for the treatment and prevention of different
types of cancers for several NSAIDs alone or in combination with current
chemotherapeutic drugs. Furthermore, an extensive review of the most
promising structural modifications is reported, such as phospho, H2S, and NO releasing-, selenium-, metal complex-, and natural
product-NSAIDs, among others. We also provide a perspective about
the new strategies used to obtain more efficient NSAID- or NSAID derivative-
formulations for targeted delivery.