Cancer seriously threatens human health. Surgery, radiotherapy and chemotherapy are the three pillars of traditional cancer treatment, with targeted therapy and immunotherapy emerging over recent decades. Standard drug regimens are mostly executed via intravenous injection (IV), especially for chemotherapy agents. However, these treatments pose severe risks, including off-target toxic side effects, low drug accumulation and penetration at the tumor site, repeated administration, etc., leading to inadequate treatment and failure to meet patients’ needs. Arising from these challenges, a local regional anticancer strategy has been proposed to enhance therapeutic efficacy and concomitantly reduce systemic toxicity. With the advances in biomaterials and our understanding of the tumor microenvironment, in situ stimulus-responsive hydrogels, also called smart hydrogels, have been extensively investigated for local anticancer therapy due to their injectability, compatibility and responsiveness to various stimuli (pH, enzyme, heat, light, magnetic fields, electric fields etc.). Herein, we focus on the latest progress regarding various stimuli that cause phase transition and drug release from smart hydrogels in local regional anticancer therapy. Additionally, the challenges and future trends of the reviewed in situ smart hydrogels for local drug delivery are summarized and proposed.

Discovered and cloned in 2000, the WW domain-containing oxidoreductase (WWOX) gene serves as a crucial tumor suppressor gene. Its expression is frequently downregulated in a wide spectrum of human malignancies, and this reduction is strongly correlated with accelerated tumor progression and poor patient prognosis. WWOX exerts its tumor-suppressive effects through direct physical interactions with numerous key signaling proteins. However, much of the current research remains in its early stages, particularly studies focusing on WWOX as a biomarker and WWOX-targeting therapies. Furthermore, there is a notable deficiency in related clinical validation, leading to uncertainties regarding clinical translation. This review specifically focuses on elucidating the significant contributions of WWOX in modulating critical oncogenic traits within cancer cells. We detail its impact on uncontrolled proliferation, invasive potential, metastatic spread, metabolic reprogramming that favors tumor growth, interactions with the immune response, and the maintenance of genetic stability. Following this exploration of WWOX’s diverse mechanistic roles in cancer biology, the review further discusses the emerging translational potential of targeting WWOX pathways, including its application as a prognostic biomarker and the development of strategies that exploit WWOX function or restoration for novel cancer therapeutics.