Bench to Bedside: New Therapeutic Approaches with Extracellular Vesicles and Engineered Biomaterials for Targeting Therapeutic Resistance of Cancer Stem Cells

Abstract

Cancer has recently been the second leading cause of death worldwide, trailing only cardiovascular disease. Cancer stem cells (CSCs), represented as tumor-initiating cells (TICs), are mainly liable for chemoresistance and disease relapse due to their self-renewal capability and differentiating capacity into different types of tumor cells. The intricate molecular mechanism is necessary to elucidate CSC's chemoresistance properties and cancer recurrence. Establishing efficient strategies for CSC maintenance and enrichment is essential to elucidate the mechanisms and properties of CSCs and CSC-related therapeutic measures. Current approaches are insufficient to mimic the in vivo chemical and physical conditions for the maintenance and growth of CSC and yield unreliable research results. Biomaterials are now widely used for simulating the bone marrow microenvironment. Biomaterialbased three-dimensional (3D) approaches for the enrichment of CSC provide an excellent promise for future drug discovery and elucidation of molecular mechanisms. In the future, the biomaterial-based model will contribute to a more operative and predictive CSC model for cancer therapy. Design strategies for materials, physicochemical cues, and morphology will offer a new direction for future modification and new methods for studying the CSC microenvironment and its chemoresistance property. This review highlights the critical roles of the microenvironmental cues that regulate CSC function and endow them with drug resistance properties. This review also explores the latest advancement and challenges in biomaterial-based scaffold structure for therapeutic approaches against CSC chemoresistance. Since the recent entry of extracellular vesicles (EVs), cell-derived nanostructures, have opened new avenues of investigation into this field, which, together with other more conventionally studied signaling pathways, play an important role in cell-to-cell communication. Thus, this review further explores the subject of EVs in-depth. This review also discusses possible future biomaterial and biomaterial-EV-based models that could be used to study the tumor microenvironment (TME) and will provide possible therapeutic approaches. Finally, this review concludes with potential perspectives and conclusions in this area.

Silicon switch: Carbon–silicon Bioisosteric replacement as a strategy to modulate the selectivity, physicochemical, and drug‐like properties in anticancer pharmacophores

“…Furthermore, it is estimated that ~400,000 children under 14 years of age are diagnosed with cancer each year across the globe, with lymphomas, retinoblastoma, renal tumors, leukemias, and soft tissue sarcomas being among the major forms of childhood cancers (Ferlay et al, 2020; Libes et al, 2023; Lupo et al, 2021; Ross & Olshan, 2004). Despite significant advances in the development of selective and targeted therapies, including tumor‐targeting chemotherapies (Chambers, 2022; Kong et al, 2022; Ojima, 2021), stem cell therapies (Escudero‐Lourdes et al, 2022; Ingavle & Das, 2022; Kuijk et al, 2022; Rouzbahani et al, 2022), and immunotherapy (Laskowski et al, 2022; Luo et al, 2022; Scott et al, 2022), cancer treatment is still heavily hampered by a high number of treatment failures, severe side effects, and rampant resistance to available therapies (Herzog et al, 2021; Mountzios et al, 2022; Orszaghova et al, 2022). Small molecules have been at the heart of cancer prognosis, management, and treatment for centuries, and the recent trend of bioisosteric replacements in medicinal chemistry can give a new life to this approach to treatment.…”