Cancer is one of the most deadly diseases among all. The treatment methods involvechemotherapy, radiotherapy and surgery, but none of them is enough to eradicate themalignancy. Despite the great progress in anti-cancer treatment achieved during the last decades,drugs resistant and treatment refractoriness still extensively persists. The anticancer chemicalstructure and their mechanism have been taken into special consideration due to resistancedeveloped by tumours in response to chemotherapeutic drugs. The different effective measuresare being exploited to increase the efficacy of selected anticancer regimen, thereby overcomingthe drug resistance. Cancer initiation, progression and emergence of therapeutic resistance needto be explored to study the evolutionary phenomena of clonal somatic cell populations 1, 2, 3.While highly proliferative cancer cell undergoing chemotherapy can also affect healthy cells bythe bystander effect. This induces apoptosis and leads to cause side effects. After surgery,chemotherapy may reduce the re-emergence of cancer. Sometimes only Chemotherapy is used totreat some cancer depending there stage and site of localization. Radiotherapy can also be usedafter chemotherapeutic treatment therapy. The stepwise progression of human cancer is clinicallyrecognised. Chemotherapy helps to control cancer and relieve any symptoms 5. Chemotherapystops and slows the growth of cancer cell which grows and divides quickly.Chemotherapy helps to control cancer and relieve any symptoms5. Chemotherapy stops andslows the growth of cancer cell which grows and divides quickly. Chemotherapy can affect theblood cells. Blood cells differentiate in the bone marrow and bursa of fabricius in birds, which isthe middle of the large bones. Chemotherapy and radiotherapy lead to increase ROS and NOS inthe cells and leads to induced apoptosis in highly proliferative cells, like haemopoietic stem cellswhich are primarily present in bone marrow. Therefore it leads to decrease in stem cell count inbone marrow and lead to weak immunity6.Multidrug –resistance involves resistance to certain antibiotics, and these antibiotics can nolonger be used to control or kill the bacteria. Many different definitions for multidrug-resistant(MDR): extensively drugs –resistant (XDR) and pan drugs –resistant (PDR) bacteria are beingused in the medical literature to characterise the different patterns of resistance found inhealthcare-associated, antimicrobial-resistant bacteria 7.The excessively active growth-signalling pathway in cancer cell makes them susceptible to awide range of drugs which target growth –signaling molecules and processes involved in cellularreplication and expression. In some cases, tumours may be refractory to treatment with somecytotoxic drugs. There are two probable causes: cancer initiation progression and the emergenceof therapeutic resistance. These are evolutionary phenomena of the clonal somatic cellpopulation. The studies in experimental microbial evolution and the theoretical work inspired bysuch studies are yielding deep insights into the evolutionary dynamics of the clonal population.Yet only a little has been a little explored in the field of cancer biology.Drugs resistance remains a major barrier to the successful treatment of cancer. Drug resistancecan arise through a number of different mechanisms, including alteration in drugspharmacokinetics and metabolism, modification of drugs target, overexpression of isotopes,topoisomerase II mutation, drugs compartmentalization in cellular organelles, altered repair ofdrug-induced DNA damage ,changes in apoptotic signaling pathways and expression proteindirectly affecting cellular drugs transport 9.The mechanism induces therapeutic resistance are multifactorial. Recent evidence has shown thatextracellular vesicle (EVs) play a very important role in mediating drugs resistance. Resistancecan arise through proteins that export drugs from the cells. The drug import into the cell reducesand very few drugs enter cells by endocytosis. Resistance to drugs that enter the cell via receptoror transporter can result in a mutation that eliminates or modify these cell surface molecules.Resistant to toxic folate analogues such as methotrexate, commonly by mutation of one or boththe folate transporter (folate binding protein and reduced folate transporter) blocks the import offolate. Resistant to nucleoside analogues have been described as the result of mutation of specificnucleoside transporter 10.In general, mechanisms of resistant are specific for the nutrient analogues and structurally relatedcompound. Some of the newer anti-cancer agent, such as immunotoxins that bind to cell surfacereceptor, cannot kill cell unless that has internalised. That generally internalised via receptor-mediated endocytosis. Cancer cell mutant that has defective endocytosis is resistance to bothtoxin and immune toxin.Surprisingly sometimes the major mechanism of multidrug-resistant in culture cancer cellinvolves the expression of energy-dependent drugs efflux pump, p-glycoprotein or the multidrugtransporter. The human gene most closely related to MDR1 is MDR2; a phosphatidylcholinetransporter expressed in liver whose defect result in an inability to form bile and progressivecirrhosis. The p-glycoprotein is the human MDR1 gene product and one of 48 known ABCtransporters in the human is a 170,000-dalton –molecular weight phophoglycoprotein consistingof two ATP binding cassettes and two transmembrane regions, each of which contains sixtransmembrane domain12. The p-glycoprotein has widely expressed in much human cancer,including cancer of the gastrointestinal tract (small and large intestine liver cancer andpancreatic), cancer of the hematopoietic system (myeloma, lymphoma, leukaemia), cancer of thegenitourinary system (kidney, ovary, testicle) and childhood cancer (neuroblastomafibrosarcoma). Every living organism has encoded within its genome many members of thisfamily and they appear to be involved not only efflux of drugs but in moving nutrients and otherbiologically important molecules in to out of and across plasma membranes and intracellularmembrane in the cell.
September 7, 2019 0 Comments