Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies.

Multiple myeloma is a hematological cancer type. For its treatment, Bortezomib has been widely used. However, drug resistance to this effective chemotherapeutic has been developed for various reasons. 2D cell cultures and animal models have failed to understand the MM disease and Bortezomib resistance. It is therefore essential to utilize new technologies to reveal a complete molecular profile of the disease. In this review, we in-depth examined the possible molecular mechanisms that cause Bortezomib resistance and specifically addressed MM and Bortezomib resistance. Moreover, we also included the use of nanoparticles, 3D culture methods, microfluidics, and organ-on-chip devices in multiple myeloma. We also discussed whether the emerging technology offers the necessary tools to understand and prevent Bortezomib resistance in multiple myeloma. Despite the ongoing research activities on MM, the related studies cannot provide a complete summary of MM. Nanoparticle and 3D culturing have been frequently used to understand MM disease and Bortezomib resistance. However, the number of microfluidic devices for this application is insufficient. By combining siRNA/miRNA technologies with microfluidic devices, a complete molecular genetic profile of MM disease could be revealed. Microfluidic chips should be used clinically in personal therapy and point-of-care applications. At least with Bortezomib microneedles, it could be ensured that MM patients can go through the treatment process more painlessly. This way, MM can be switched to the curable cancer type list, and Bortezomib can be targeted for its treatment with fewer side effects.

Autophagy-related mechanisms for treatment of multiple myeloma.

Multiple myeloma (MM) is a type of hematological cancer that occurs when B cells become malignant. Various drugs such as proteasome inhibitors, immunomodulators, and compounds that cause DNA damage can be used in the treatment of MM. Autophagy, a type 2 cell death mechanism, plays a crucial role in determining the fate of B cells, either promoting their survival or inducing cell death. Therefore, autophagy can either facilitate the progression or hinder the treatment of MM disease. In this review, autophagy mechanisms that may be effective in MM cells were covered and evaluated within the contexts of unfolded protein response (UPR), bone marrow microenvironment (BMME), drug resistance, hypoxia, DNA repair and transcriptional regulation, and apoptosis. The genes that are effective in each mechanism and research efforts on this subject were discussed in detail. Signaling pathways targeted by new drugs to benefit from autophagy in MM disease were covered. The efficacy of drugs that regulate autophagy in MM was examined, and clinical trials on this subject were included. Consequently, among the autophagy mechanisms that are effective in MM, the most suitable ones to be used in the treatment were expressed. The importance of 3D models and microfluidic systems for the discovery of new drugs for autophagy and personalized treatment was emphasized. Ultimately, this review aims to provide a comprehensive overview of MM disease, encompassing autophagy mechanisms, drugs, clinical studies, and further studies.

Biomedical Applications of Microfluidic Devices: A Review.

Both passive and active microfluidic chips are used in many biomedical and chemical applications to support fluid mixing, particle manipulations, and signal detection. Passive microfluidic devices are geometry-dependent, and their uses are rather limited. Active microfluidic devices include sensors or detectors that transduce chemical, biological, and physical changes into electrical or optical signals. Also, they are transduction devices that detect biological and chemical changes in biomedical applications, and they are highly versatile microfluidic tools for disease diagnosis and organ modeling. This review provides a comprehensive overview of the significant advances that have been made in the development of microfluidics devices. We will discuss the function of microfluidic devices as micromixers or as sorters of cells and substances (e.g., microfiltration, flow or displacement, and trapping). Microfluidic devices are fabricated using a range of techniques, including molding, etching, three-dimensional printing, and nanofabrication. Their broad utility lies in the detection of diagnostic biomarkers and organ-on-chip approaches that permit disease modeling in cancer, as well as uses in neurological, cardiovascular, hepatic, and pulmonary diseases. Biosensor applications allow for point-of-care testing, using assays based on enzymes, nanozymes, antibodies, or nucleic acids (DNA or RNA). An anticipated development in the field includes the optimization of techniques for the fabrication of microfluidic devices using biocompatible materials. These developments will increase biomedical versatility, reduce diagnostic costs, and accelerate diagnosis time of microfluidics technology.

In Vitro Human Cancer Models for Biomedical Applications.

Cancer is one of the leading causes of death worldwide, and its incidence is steadily increasing. Although years of research have been conducted on cancer treatment, clinical treatment options for cancers are still limited. Animal cancer models have been widely used for studies of cancer therapeutics, but these models have been associated with many concerns, including inaccuracy in the representation of human cancers, high cost and ethical issues. Therefore, in vitro human cancer models are being developed quickly to fulfill the increasing demand for more relevant models in order to get a better knowledge of human cancers and to find novel treatments. This review summarizes the development of in vitro human cancer models for biomedical applications. We first review the latest development in the field by detailing various types of in vitro human cancer models, including transwell-based models, tumor spheroids, microfluidic tumor-microvascular systems and scaffold-based models. The advantages and limitations of each model, as well as their biomedical applications, are summarized, including therapeutic development, assessment of tumor cell migration, metastasis and invasion and discovery of key cancer markers. Finally, the existing challenges and future perspectives are briefly discussed.