Anticancer drugs resistance is a complex process that arises from altering in the drug targets. Advances in the DNA microarray, proteomics technology and the development of targeted therapies provide the new strategies to overcome the drug resistance. Although a design of the new chemotherapy agents is growing quickly, effective chemotherapy agent has not been discovered against the advanced stage of cancer (such as invasion and metastasis). The cancer cell resistance against the anticancer agents can be due to many factors such as the individual’s genetic differences, especially in tumoral somatic cells. Also, the cancer drug resistance is acquired, the drug resistance can be occurred by different mechanisms, including multi-drug resistance, cell death inhibiting (apoptosis suppression), altering in the drug metabolism, epigenetic and drug targets, enhancing DNA repair and gene amplification. In this review, we outlined the mechanisms of cancer drug resistance and in following, the treatment failures by common chemotherapy agents in the different type of cancers.
Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis.
Tissue engineering is a rapidly-growing approach to replace and repair damaged and defective tissues in the human body. Every year, a large number of people require bone replacements for skeletal defects caused by accident or disease that cannot heal on their own. In the last decades, tissue engineering of bone has attracted much attention from biomedical scientists in academic and commercial laboratories. A vast range of biocompatible advanced materials has been used to form scaffolds upon which new bone can form. Carbon nanomaterial-based scaffolds are a key example, with the advantages of being biologically compatible, mechanically stable, and commercially available. They show remarkable ability to affect bone tissue regeneration, efficient cell proliferation and osteogenic differentiation. Basically, scaffolds are templates for growth, proliferation, regeneration, adhesion, and differentiation processes of bone stem cells that play a truly critical role in bone tissue engineering. The appropriate scaffold should supply a microenvironment for bone cells that is most similar to natural bone in the human body. A variety of carbon nanomaterials, such as graphene oxide (GO), carbon nanotubes (CNTs), fullerenes, carbon dots (CDs), nanodiamonds and their derivatives that are able to act as scaffolds for bone tissue engineering, are covered in this review. Broadly, the ability of the family of carbon nanomaterial-based scaffolds and their critical role in bone tissue engineering research are discussed. The significant stimulating effects on cell growth, low cytotoxicity, efficient nutrient delivery in the scaffold microenvironment, suitable functionalized chemical structures to facilitate cell-cell communication, and improvement in cell spreading are the main advantages of carbon nanomaterial-based scaffolds for bone tissue engineering.