**8. The role of extracellular vesicles in drug resistance in cancers**

Due to an improved effectiveness of cancer therapies lately, there have been an increase in the survival rate of diagnosed cases [143]. Some tumors however, remain non-responsive to available treatment regimen resulting in patients going through relapse. Many cancer drugs work by causing damage in the DNA of dividing cells, which eventually result in their apoptotic death. Research has shown that some cells gain the ability to effectively repair the damage caused to them or lose the capacity to recognize apoptotic signals which renders them less capable of submitting to programmed cell death [144, 145]. Such cells become more likely to grow resistant.

#### *Extracellular Vesicles as Biomarkers and Therapeutic Targets in Cancers DOI: http://dx.doi.org/10.5772/intechopen.101783*

The failure of treatment in general and for that matter cancer treatment could occur through various ways. It could happen through drug metabolism alterations, or changes in the efflux and/or absorption of drugs from target cells. In addition to this, the ability of drugs to induce mutations and the inhibition of cellular apoptotic pathways are all ways by which drug resistance could occur. Once acquired, the multidrug resistance of cancer drugs can lead to resistance to other drugs of different structural make-up or target.

Cancer cells have specific characteristic genetic make-up together with varying expressions of tumor suppressor genes and oncogenes. This makes them respond distinctively to various drugs. Interactions exist between host and tumor microenvironment together with changes in these genetic factors which contribute to drug resistance [146, 147]. Drug resistance represents a daunting challenge in the treatment of cancer patients. There are two types of drug resistance: de novo drug resistance, which refers to the insensitivity of cancer cells to chemotherapy before receiving drug treatment, and acquired resistance, which refers to the acquired drug resistance of cancer cells after being treated [148]. Understanding drug resistance has not been an easy task because of how complex and challenging their supporting molecular mechanisms are [149–152]. In fact, the source of resistance of a drug in a person may be very different from that of another individual because of the variations in fundamentals of different cellular processes. Playing an important role in drug resistance are extracellular vesicles. They mediate cancer drug resistance such that cells that secrete more of these vesicles show higher level of resistance than those that secrete less [153].

Recently, there are many studies concerning the role and effects of EVs in disease control and drug resistance. They have been identified to show a profound role in the development of chemo-insensitivity and drug resistance [148]. The study into their characteristics increased after they were discovered to be involved aspects of cancer progression including in proliferation, tumorigenesis, angiogenesis, and invasiveness [154–156]. In cancer drug resistance analysis, therapeutic targets are very much implicated in the development of resistance. The mediation of drug resistance by EVs takes place through a number of mechanisms. One is by the reduction of the effective concentration of cytotoxic drugs at target sites through the behavior of EVs acting as a pathway for the sequestration of such drugs. That is, resistance can arise when there is an up-regulation of vesicles that export drugs from cells or a reduction in those carriers that import drugs into the cells [157–161]. The results of such changes are the alteration in the concentrations of chemotherapeutics at the active sites. These vesicles may also act as decoys, carrying membrane proteins and capturing monoclonal antibodies intended to target receptors at the cell surface. They can also mediate cross-talk between cancer cells and stromal cells in the tumor microenvironment, leading to tumor progression and acquisition of therapeutic resistance. Apart from their role in drug resistance within a cell, EVs can transfer the resistance from a cell to another cell [162].
