Multi Drug Resistant (MDR) for Cancer Management

Significance: understanding the mechanism of drug resistance in cancer leads to developing more potent drugs.

With the hopes of curing the patient’s afflictions, these newly grown cells would then be transplanted into the patient. With this approach come major problems such as the formation of tumours, which is caused by the distinguishing trait of stem cells. Because stem cells are able to divide for an unlimited amount of time, it has been found that the cells will not know when to stop dividing and they will continue to divide even after being transplanted into the patient (Herold 48). This form of treatment is counterproductive, as uncontrollable cell division will produce tumours and potentially cause cancer, which is one of the ailments that stem cell research promises to cure.

Antimicrobial resistant has been called one of the world's most pressing public health problems. Every time a person takes antibiotics, sensitive bacteria are killed, but resistant ones may be left to grow stronger and multiply. Although antibiotics can help treat bacterial infections, a possible side effect is that they can strengthen certain bacterial strains. Antibiotics are supposed to be used for bacterial infections, but are wrongly being used for both viral and bacterial infections. When we use antibiotics on viral infections, deadly bacteria multiplies and becomes stronger. We can fix this problem by using antibiotics for bacterial infections only.

Cancer is a disease caused by an uncontrolled division of abnormal cells. The DNA sequence in cells can be changed as a result of copying errors during replication. If these changes whatever their cause are left uncorrected, both growing and non-growing somatic cells might gain many mutations that they could no longer function. The relevance of DNA damage and repair to the generation of cancer was obvious when it was recognized that everything that causes cancer also cause a change in the DNA sequence. Tumor suppressor genes are protective genes and normally they limit cell growth by monitoring the speed of cell division, repair mismatched DNA and control when a cell dies. When a tumor suppressor gene is mutated cells grow

Cancer cells displayed marked alterations in pro-growth signaling pathways and key metabolic pathways relative to non-tumorigenic differentiated cells, often due to loss of tumor suppressor genes and oncogenic driver mutations. The remodeled signaling and metabolic profiles of cancer cells support not only their aberrant proliferation, but also their survival. Further factors such as intra-tumoral heterogeneity, altered redox status, and epigenetic modifications all contribute to the ability of certain tumors to develop drug resistance and persist under standard treatments.

Compound 3a was selected by the National Cancer Institute (NCI) USA for anticancer screening with the NCI code D-785902/1. Compound 3c was found in the already tested cancer candidates in the NCI data base under NCI code NSC: 650353[42]. Both candidates were screened on human tumour cell lines at 10-5 M at the 60-Cell-Line Screenings of the Developmental Therapeutics Program (DTP) of the National Cancer Institute (NCI, Bethesda, Maryland, USA) under the drug discovery program of the NCI. The 60-cell-line-screening of the NCI includes 60 different tumour cell lines, the nine various organs and tumour types derived (leukaemia, non-small-cell lung cancer, colon cancer, CNS cancer, melanoma,

Besides fetal stem cells, adult stem cells are also researched for new therapies yet are not as effective. According to the National Institutes of Health (2015), the stem cells obtained from an embryo are analyzed in order “to identify how undifferentiated stem cells become the differentiated cells that form the tissues and organs.” Many diseases are caused by an abnormality of cell division and cause the body to decline in health over time. The most common disease of abnormal cell growth is cancer, which destroy body tissues. Although there are

The ability to manipulate the stem cell corresponding to a specific organ/tissue remains important. A type of stem cell that can be manipulated is the embryonic stem cell. These stem cells descend from embryos aging from three to five days (Watt) (Driskell). During earlier stages, scientists describe embryonic stem cells as “blastocysts” which contain over one-hundred and fifty cells (Watt) (Driskell). They duplicate into more cells or transform to any cell located in the body (Watt) (Driskell). This “duplication” allows embryonic stem cells to regenerate and repair diseased tissues. Embryonic stem cells gain importance in cancer treatments—if doctors diagnose patients with leukemia, then during chemotherapy, the doctor can infuse embryonic stem cells into the body. Since the cells are young, they can repair the targeted cell, aiding cancer treatments and the patient. In addition, this technique is used with another type of embryonic stem cell called “pluripotent stem cells”. Pluripotent stem cells originate as inner mast cells (cells

The journal article describes the data that was collected by the recent test of the drug, Rociletinib. The drug is described as a new development that has potential for treating the advanced cancerous tumors. The specific tumors that were analyzed had already developed a resistance to the medicine. Its clinical trials were done on a sample size of 130 patients. The 57 patients of the study that received the drug showed positive results in their treatments of NSCLC.

The type of cancer I chose to write about is called acute lymphoblastic leukemia. Acute lymphoblastic leukemia is developed through damaged bone marrow and blood cells. Stem cells form blood cells, these stem cells that form white cells start out as cells then generate into blast cells, or also known as lymphoblast. Lymphoblast then produce a cell a type of white blood cell known as lymphocytes. This damaged cell then becomes a leukemic cell and multiples into billions of cells leukemic lymphoblast cells. This then causes the number of healthy blood cells to drastically lower. The origin of the word "acute" comes from the fact that the disease progresses rapidly and creates immature blood cells, rather than mature ones. It also can be called acute lymphocytic leukemia. Acute lymphoblastic leukemia is a

The established definition of rituximab resistance is the lack of response or the progression within 6 months of treatment to a rituximab-containing regimen.11 Obvious disease progression during rituximab therapy is the most clearly defined form of resistance. Patients who may experience tumor shrinkage have some degree of rituximab sensitivity but are often classified as “resistant” if they fail to achieve either a partial or complete response. Numerous pathways of tumor resistance have been elucidated with conventional chemotherapeutic agents. In some cases, these discoveries have translated into specific interventions aimed at preventing or overcoming tumor resistance.11 Surprisingly, little is known about the determinants of responsiveness

According to the National Institute of Health, “Stem [cells] in tumors cause 1:250,000 cells to be cancer cells”(Goldthwaite). Statistics produced from this study, conducted by the National Institute of Health, prove the danger of cancer cells forming from stem cell therapy. Furthermore, the same study reveals “CSCs [cancer stem cells] arise from stem cells” (Goldthwaite). These discoveries show that if humans use stem cells than cancer stem cells can arise as a result. There is a direct correlation between stem cells and cancer stem cells. Unless stem cell research cease, many humans will develop

Ovarian cancer is the seventh most common cancer in women, accounting for almost one-third of invasive malignancies of the female genital organs, and has remained the leading cause of death from gynecological cancers (105). Multidrug resistance (MDR) is one of the most important mechanisms, seen in various cancers, resistant to chemotherapy drugs. Overexpression of the membrane efflux proteins has a major role in the occurrence of this mechanism (106). Several members of the multidrug resistance proteins (MRPs) family, especially MRP1 and MRP2 are able to transport anticancer drugs out of the cells and present in many different types of tumors, and therefore assumed to cause MDR (107).

Genomic heterogeneity in tumors of different patients, it becomes increasingly evident that the diversity of cell types in tumor cell populations also likely plays a key role in drug susceptibility. I.e. subsets of tumor cell with distinct States of differentiation or with properties of "stem cells" may have distinctive sensitivity to drugs.(36, 37) In vitro studies have shown that this cellular heterogeneity can influence the response to treatment with anti-cancer agents.

Gemcitabine has a gold drug standard and has very similar activation step as of ara-C but with more complicated mechanism and with more cellular targets. Gemcitabine resistance is the biggest problem in the chemotherapy of cancer patients, alterations in the cellular target of the gemcitabine results in decreased sensitivity of the drug. There many factors involved in the resistance of gemcitabine and thus, a thus a thorough study is required for better understanding of the mechanisms determining its activation and development of resistance. This paper / article / review deals with the mechanisms involving pharmacology of gemcitabine. [ref 2 & 3]