Beyond stiffness: deciphering the role of viscoelasticity in cancer evolution and treatment response.

There is increasing evidence that cancer progression is linked to tissue viscoelasticity, which challenges the commonly accepted notion that stiffness is the main mechanical hallmark of cancer. However, this new insight has not reached widespread clinical use, as most clinical trials focus on the application of tissue elasticity and stiffness in diagnostic, therapeutic, and surgical planning. Therefore, there is a need to advance the fundamental understanding of the effect of viscoelasticity on cancer progression, to develop novel mechanical biomarkers of clinical significance. Tissue viscoelasticity is largely determined by the extracellular matrix (ECM), which can be simulated in vitro using hydrogel-based platforms. Since the mechanical properties of hydrogels can be easily adjusted by changing parameters such as molecular weight and crosslinking type, they provide a platform to systematically study the relationship between ECM viscoelasticity and cancer progression. This review begins with an overview of cancer viscoelasticity, describing how tumor cells interact with biophysical signals in their environment, how they contribute to tumor viscoelasticity, and how this translates into cancer progression. Next, an overview of clinical trials focused on measuring biomechanical properties of tumors is presented, highlighting the biomechanical properties utilized for cancer diagnosis and monitoring. Finally, this review examines the use of biofabricated tumor models for studying the impact of ECM viscoelasticity on cancer behavior and progression and it explores potential avenues for future research on the production of more sophisticated and biomimetic tumor models, as well as their mechanical evaluation.

Mimicking the Tumor Niche: Methods for Isolation, Culture, and Characterization of Cancer Stem Cells and Multicellular Spheroids.

Cancer stem cells (CSCs) play a significant role in driving several tumor hallmarks. Their behavior and tumor progression are strictly related to the tumor microenvironment (TME). The dynamic interplay between CSCs and TME drives metastasis, chemoresistance, and disease relapse. In this chapter, we describe different techniques and protocols for isolating, culturing, and characterizing CSCs and we explain the methodology for the culture of multicellular spheroids comprising CSCs.

Unraveling the Potential of miRNAs from CSCs as an Emerging Clinical Tool for Breast Cancer Diagnosis and Prognosis.

Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC stem cells (BCSCs). This small subpopulation within the tumor possesses unique characteristics, including tumor-initiating capabilities, contributes to treatment resistance, and plays a role in cancer recurrence and metastasis. In recent years, microRNAs (miRNAs) have emerged as potential regulators of BCSCs, which can modulate gene expression and influence cellular processes like BCSCs' self-renewal, differentiation, and tumor-promoting pathways. Understanding the miRNA signatures of BCSCs holds great promise for improving BC diagnosis and prognosis. By targeting BCSCs and their associated miRNAs, researchers aim to develop more effective and personalized treatment strategies that may offer better outcomes for BC patients, minimizing tumor recurrence and metastasis. In conclusion, the investigation of miRNAs as regulators of BCSCs opens new directions for advancing BC research through the use of bioinformatics and the development of innovative therapeutic approaches. This review summarizes the most recent and innovative studies and clinical trials on the role of BCSCs miRNAs as potential tools for early diagnosis, prognosis, and resistance.