Deciphering Drug Resistance: Investigating the Emerging Role of Hyaluronan Metabolism and Signaling and Tumor Extracellular Matrix in Cancer Chemotherapy.
Daiana L VitaleArianna ParnigoniManuela ViolaEvgenia KarousouIna SevicPaola MorettoAlberto PassiLaura D AlanizDavide VigettiPublished in: International journal of molecular sciences (2024)
Hyaluronan (HA) has gained significant attention in cancer research for its role in modulating chemoresistance. This review aims to elucidate the mechanisms by which HA contributes to chemoresistance, focusing on its interactions within the tumor microenvironment. HA is abundantly present in the extracellular matrix (ECM) and binds to cell-surface receptors such as CD44 and RHAMM. These interactions activate various signaling pathways, including PI3K/Akt, MAPK, and NF-κB, which are implicated in cell survival, proliferation, and drug resistance. HA also influences the physical properties of the tumor stroma, enhancing its density and reducing drug penetration. Additionally, HA-mediated signaling contributes to the epithelial-mesenchymal transition (EMT), a process associated with increased metastatic potential and resistance to apoptosis. Emerging therapeutic strategies aim to counteract HA-induced chemoresistance by targeting HA synthesis, degradation, metabolism, or its binding to CD44. This review underscores the complexity of HA's role in chemoresistance and highlights the potential for HA-targeted therapies to improve the efficacy of conventional chemotherapeutics.
Keyphrases
- signaling pathway
- extracellular matrix
- pi k akt
- epithelial mesenchymal transition
- cell cycle arrest
- oxidative stress
- cell proliferation
- papillary thyroid
- mental health
- squamous cell carcinoma
- small cell lung cancer
- cell death
- induced apoptosis
- working memory
- cancer stem cells
- immune response
- transforming growth factor
- childhood cancer
- adverse drug