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Development of Cancer Drug Resistance

Table of Contents

Development of cancer drug resistance………………………………………………………………………………. 4

Introduction……………………………………………………………………………………………………………………. 4

Cancer Drug Resistance & Role of Epigenetic……………………………………………………………………. 5

The Treatment and Relapse of Cancer……………………………………………………………………………….. 6

Mechanism of Drug Resistance…………………………………………………………………………………………. 6

Cross-Resistance Development…………………………………………………………………………………………. 8

How do the Resistance Cells Develop?……………………………………………………………………………… 9

Treating Drug Resistance in Cancer…………………………………………………………………………………. 11

Inactivation of Drugs………………………………………………………………………………………………….. 11

Variation in Drug Targets……………………………………………………………………………………………. 12

Drug Efflux………………………………………………………………………………………………………………. 13

Damage repair of DNA………………………………………………………………………………………………. 13

Inhibition of Cell Death………………………………………………………………………………………………. 14

EMT & Metastasis……………………………………………………………………………………………………… 15

Heterogeneity of Cancer Cell………………………………………………………………………………………. 15

Conclusions………………………………………………………………………………………………………………….. 16

References……………………………………………………………………………………………………………………. 17

Abstract

            Cancers are equipped with a unique ability to develop resistance against the traditional therapies hence, more and more research and development in treatment methods are required on regular basis due to their ever increasing ability to prevail. The paper describes various mechanisms that are adopted by the cancer cells to resist the treatment and therapy methods. These mechanisms include drug metabolism and transport, amplification and mutation of the drug targets. 

This also includes genetic rewiring of that can lead to apoptosis of impaired nature. This research paper also provides the current knowledge of various mechanisms that enable the resistance to drugs such as repair of DNA damage, alteration of drug target, drug inactivation, EMT and metastasis and drug efflux. The paper also outlines how these cancer cells inherit heterogeneity and what role it has to play in their resistance development.

In addition to this some of the resistance, I develop into multidrug resistance which further worsens the situation for the clinical methods to tackle the issue. In this paper, we have also discussed multiple insights in order to understand various processes that can impact the next generation of cancer therapies and treatments. In the end, the paper concludes the discussion on the best treatment options that can be used to reduce the drug resistance nature of the cancers and their cells and this can give positive direction to the research and devilment in this area.

Development of cancer drug resistance

Introduction

            Resistance to drugs is a very common phenomenon which is enabled within the diseases when pharmaceutical treatments and therapies have no effect on the infected cells. The ideology was first brought to the world when bacteria became drug resistance to certain antibiotics but after that, a similar issue was detected within the other disease cells and one of them was cancer as well. There are a number of methods to tackle the drug resistant issue which will be elaborated in the following text. In the year 1961, Frei and Freireich introduced a method in which a combination of four drugs each with high dosage was applied for the purpose of treating pediatric leukemia. There were known threats that were associated with the high dosage of all four drug combination however, the treatment were very much successful and the leukemia cells did not return (Ahmad, 2014).

However, the success did not last for long and there were plenty of cases where the patients relapsed. In fact, the redeveloped cells were more vigorous in nature and the developed cancer cells displayed no response and the cells invaded the brain blood as well and since then there is not much development that has been made as the disease continues to colonize other body organs and are developed into a more vigorous form as well. However, in the recent times, there have been a number of cases where the cancer cells have been treated successful especially in the cases of acute promyelocytic leukemia and chronic myeloid leukemia. There are a number of success stories of pediatric leukemia as well as testicular cancer and Hodgkin’s lymphomas (Akhdar, Legendre, Aninat, & Morel, 2012). 

Cancer Drug Resistance & Role of Epigenetic

            Epigenetic modifications, which have the tendency to affect carcinogenesis, are one of the most important sets of mechanisms that have a crucial role to play in causing the cancer resistance. The major kinds of epigenetic variation include histone modification through methylation or acetylation or with DNA methylation. The process of DNA methylation involves binding of methyl groups   for the purpose of cytosines in the regions which are known as CpG islands at CG dinucleotides.  These are found in the promoter regions of the upstream gene. On the other hand, the histone modification includes the opening of chromatin while DNA methylation or deacetylation closes the chromatin. However, the epigenetic modification can be reversed and this can be used to counter the ability of the cancer cells to develop resistance (Chen, 2014).

Many of the treatments and mechanisms are influenced by epigenetic variations. Many still believe that these methods are developed from the four drug combinations that were used in the early 1960s. These epigenetic modifications can also have a positive influence on damage repair of DNA. The enzyme that is used for DNA repair shows the disintegration of the cancerous cells using the alkylating agents of chemotherapy.  The cells of human breast cancer can also display resistance to drugs and therapies using the epigenetic changes and these mediated forms are also observable in other forms of cancer as well. For example, the cells of melanoma are nonresponsive to chemotherapy and they have the tendency to develop resistance to fotemustine (Dinsa & Melesie, 2014).

The Treatment and Relapse of Cancer

Epigenetics have a major role to play in cancer stem cells and their growth. Hence focusing on addressing this issue can reduce the relapse of cancer. It is very much reasonable to speculate that a normal trigger can initiate the growth of the cancerous cells. Hence, reversing the epigenetic modification can reduce the formation of the progenitor cells hence, reducing the relapse chance. Nevertheless, the design and development of the drug to treat cancer have to be fully effective and for this, a better understanding of the mechanisms by which the cancer cells can be cured and their further growth can be stopped. There are a number of treatments that can be used for this purpose. These treatments include the mutation of extracellular receptors, modification of drug transport as well as mutation and amplification of drug targets (Eid, El-Readi, Fatani, Eldin, & Wink, 2015).

There are number o0of other methods that care used by the medical experts and will be provided in the following text. Therefore, the reversal of the epigenetic modifications has a major role to play in stopping the growth and development of the progenitor cells and the primary focus of all the medical treatments should be in this area. This will prevent other body parts as well to develop any formation of invaded cells and will permanently halt their production within the body. This is the reason why the medical experts now tend to focus on the epigenetic modifications that contribute a lot towards the relapse of the progenitor cells. This is a better way to adopt the treating methods for relapsing cancer (Foo & Michor, 2014).

Mechanism of Drug Resistance

            Acquired resistance, as well as primary resistance, may result from the variations that have been developed due to drug metabolism such as improved detoxification and sequestrations or even due to drug target alterations. Drug metabolism is probably the most researched part of drug resistance and this includes detoxification, uptake, and efflux. The selection of the medium that is used to enter the drug into the cells completely depends on upon the chemical nature. It majorly facilitates the usage of receptors which are bound and transferred without entering into the cells or they may use the transporter to promote cellular entry (Housman, et al., 2014).

At this stage, extracellular receptors are smoothened by the reduced expression the transporters that can be used here include nucleoside transporter or folate transporters. However, this can negatively influence the uptake of the cyclopamine and various other drugs including toxic folate analogs like methotrexate and nucleoside drugs like cytarabine. However, the enhanced drug efflux can increasingly cause frequent expression of membrane transport using ATP binding cassette. For the purpose of exerting the cytotoxic effects, anti-cancer drugs have to go for metabolism activations. To understand this concept considers cytarabine which is also known as AraC. Cytarabine is a nucleoside drug that is very commonly used in the therapies and treatments of acute myelogenous leukemia (Hu, Li, Gao, & Cho, 2016).

Cytarabine facilitates the initial phosphorylation through deoxycytidine kinase to cytarabine-monophosphate that frequently phosphorylated the cytarabine triphosphate. For reducing the effects of the drugs, these cancer cells develop a form of resistance by decreasing the activation and triggering of drugs and their effects. This takes place either by down-regulation or the mutation the enzymes that are present in the metabolic pathways. The metabolic pathways in the case of cytarabine are deoxycytidine kinase. The inactivation of the drug may also have a major role to play in the development of drug resistance. For instance, these mechanisms also include the conjugation of drug to GSH. GSH is a powerful anti-oxidant which protects the cells in case of any devastating effects of the highly reactive oxygen species (Koushik, Rao, Kumar, & Karthikeyan, 2016).

The conjugation of drug to GSH and to platinum drugs including cisplatin and oxaliplatin can be used in curing the cancer cells and can also be used to substrate for the ATP binding cassette transporters and this improves the performance of the drug efflux treatment and its outcomes as well. The binding of the platinum drugs particularly cisplatin to metallothionein which is a tiny protein rich in cysteine can also be used as another type of method that can be used as inactivation of the drug. Many of the cancer cells tend to develop an over dependency on an oncogene which can also be named as an addiction of oncogene. Focusing on these types of oncogenes may allow development of new techniques in targeted treatments as well as therapies. The most common examples of these targeted therapies include trastuzumab which focuses on human epidermal growth factor receptor 2 (HER 2), imatinib which targets the ABL/BCR tyrosine kinase in CML and gefitinib as well as erlotinib that focuses on epidermal growth factor receptor (EGFR) (Koushik, Rao, Kumar, & Karthikeyan, 2016).

Cross-Resistance Development

            The resistance to one drug may develop into the resistance to other drugs as well and this is another important feature of drug resistance to looking at. This can be understood with help of an example of loss of a drug transporter might direct the structurally complex compounds that use this transportation or in other words, the ATP-binding cassette transporters may get elevated by the resulting therapy and this can directly influence the efficacy of all other compounds as well. As the poor chemotherapy response can directly be influenced by multidrug resistance phenotypes the development of techniques can be used to overcome the underlying issues. Hence the drugs that are not recognized by the transporters completely avoid efflux as well as inhibitors (Liu, 2009).

However, resistance doesn’t go useless here the alternative technique to treat the drug progeny uses and emphasizes through Darwinian selection procedure which is to identify the base where the resistance to first provided drug initiated a hypersensitivity to the cytotoxic agent alternatively. Collateral sensitivity is referred to as synthetic lethality because same genetic alteration that cell resistant to a particular drug and sensitizes it to another drug as well. Hence it is very important for the medical experts and scientists because development of resistance to one drug can develop resistance to other drugs as well and this can halt the process of curing the cancer cells and for this purpose the chemical nature of all the different compounds used in this process have to be critically analyzed so that the methods of treatment and therapies can be improved (Okon, 2016).

How do the Resistance Cells Develop?

            Human cancers and their development is a complex process that involves numerous stages. These stages include epigenetic modifications that have been developed over time as well as genetic alterations. This results in the development of single tumor that is comprised of the non-homogametic cell population which has diverse genetic fingerprints. As the development of tumor progresses some of the cells undergo various genetic modifications. These modifications have a superior level of growth advantage. The best example of this case is the cells of breast cancer which have various tumor heterogeneities. According to a study, approximately 98% of epithelial breast carcinomas have intra-tumor diversities and due to this innate level of heterogeneity, the cancer cells demonstrate a high level of resistance (Rueff & Rodrigues, 2016).

Hence, it can be easily understood that the cancer cells demonstrate the same characteristics as provided by the Darwinian law of evolution. The focus should be on those cell populations that are most adaptive and display very heterogeneous tendencies. They form clones and these clones then begin to populate the tumor and make it extremely resilient to any treatment or therapy. This selection process can be done using two different mechanisms. One is the cellular population emergence after the selection of the drug binding while the second method includes stochastic modification acquisitions within the drug transporters. Two models including CSC model or the cancer stem cell model and EMDR model or environment mediated drug resistance model can be used to explain this process and they both are mutually exclusive as well. The rare populations of the cancer cells in CSC model are equipped with tumor-initiating characteristics. The EMDR model develops resistance as the cancer cells interact with the close by microenvironment and enter into a dormant state and they diminish the effects of the treatment or the therapy (Sameen, 2015).

These cells remain in their shelters during the imposed pressure and continue with their genetic variations till the time they acquire permanent resistance phenotype. The surviving populations of the cancer cells can play their role in Minimal Residual Disease or MRD thus, contributing towards relapse. In the EMDR model, metastatic epithelial malignancies, as well as hematopoietic epithelial malignancies, can be mediated with help of soluble and adhesive microenvironment elements. One of the mediators for this resistance is interleukin-6 which is also known as IL-6. This mediator has increased the level of secretion and it will be correlated with various resistances from cytotoxins in all in vivo and in-vitro models. At the molecular level, this procedure can take place in numerous scenarios which include improves stability and modified the subcellular distribution of all the protein and cell cellular moderators as well as degradation of apoptotic proteins as well. In this case, the cancer cells have a tendency to use fibronectin adhesion from the surrounding environment for the purpose of limiting endogenous levels. Hence, these two models can be used to understand and explain various issues related to the development of the cancer cells within the bodies. This can lead to the development of sound techniques and methodologies to cure the disease and prevent their relapse (Sebens & Schäfer, 2012).      

Treating Drug Resistance in Cancer

Inactivation of Drugs

Medications are changed in the body by an assortment of pathways to acquiesce pharmacologically dynamic or concealed metabolic items. A few rejoinders result in dynamic metabolites and some of the unoccupied items. Contingent upon the configuration of the medication, a similar response may frame self-motivated or inert metabolites. Despite the fact that mixes are at last changed by catalysts, there are numerous components that adjust the chemical action, for example, inhibitors, hormones, tissue limitation, and vitamins (Sebens & Schäfer, 2012). 

In spite of an assortment of cases of the contact of the human being gastrointestinal microbiome on prescription satisfactoriness and lethality, there is repeatedly a disjointed intellectual capacity of the elementary classifications. Here, we investigate the inactivation of the heart meditates digoxin by the reduced to ashes Actinobacterium Eggerthella lenta. The Transcriptional silhouette, comparative genomics, and culture-based measures discovered and uncovered a cytochrome-encoding operon up intended for by digoxin, unemotional by arginine, malinger in nonmetabolizing E. lenta sprains, and clairvoyant of digoxin inactivation by the individual reduced to ashes microbiome. It is the fact that inactivation of drugs is quite necessary for the solution of this project.  On the other hand, it is also viewable that everyone wants to become safe, healthy, and fearless from cancer. Therefore, the best way is to inactivate the drugs for resistance from cancer (Ullah, 2008). 

Variation in Drug Targets

 It is the fact that Individual fickleness in medication practicability and prescription health is a worth mentioning test in contemporary irrefutable put into practice. In addition, the sedated advancement, and medication control is the part of this particular drug targets. It is imperative to understand that investigations of pharmacokinetics have given satisfactory cases of contributory relationships in the midst of genotypes and prescription rejoinder to characterize phenotypic varieties of clinical significance in prescription treatment. On the other hand, the merger of pharmacokinetics and human genomics as of belatedly has extensively accelerated the surprise of new transmissible varieties (Wang, 2015).

It will possibly bring about fickleness in prescription rejoinder. Even though the express aggregation of in a row on genome-malady and genome-tranquilize family and association, there comes into view the trust of the individualized drug. On the other hand, we assessment late press forward in the conception of hereditary dedication to real personage fickleness in prescription handling with contemplating on a transmissible multiplicity of tablets target, dignified incorporation system, put under sedation transfer, complaint vulnerability, and prescription wellbeing. It is the fact that Difficulties to potential pharmacokinetics and its elucidation into individualized pills, put under sedation expansion, and bearing is scrutinized. For instance, wisdom on genetic determinants of woe pathogenesis and prescription hullabaloo, for the most part, those of multipart infectivity and prescription reaction, is not commonly easily reached. Concerning the abundant eminence multiplicity from genomic sequencing to detached phenotypes may not be comprehensible (Zahreddine & Borden, 2013).

Drug Efflux

The drug efflux is known to be a quite famous way to resist the chances of cancer. It is very imperative to understand that it is quite important in the medical sector. Most of the researchers are working hard to improve the system of drug efflux. It is very important for the well-being of the people and one should plan for the betterment of the community.  It is the fact that the planning needs to be long term.  We are moving speedily to the modern world and we must prepare ourselves for the better future in order to fight with diseases (Ahmad, 2014). 

The drug efflux is the broader concept for the people in order to modernize and correct the setup on medical terms. One can understand that cancer is major disease and we cannot get away after closing the eyes. Therefore, it has become very important to plan the setup medically and according to the principles of cancer treatment. There are many companies and research centers working on the latest researches for prevention of cancer and one can understand the various diseases under the umbrella of cancer.  Therefore, it is obvious that drug efflux has the main role and key importance in the cancer treatment (Eid, El-Readi, Fatani, Eldin, & Wink, 2015).

Damage repair of DNA

It is very imperative to understand that cancer is the major disease in the modern world.  Although, the treatment is there but still there are many things to do in the future. We cannot take the credit away from the researchers and physicians as well. They are doing everything for the better health of the human beings.  They are providing services to the patients and humanity and making things better.  The research in the field of cancer has portrayed the fact that there could be a damage occur in the process of treatment of cancer (Okon, 2016).

On the other hand, one would have to realize and understand that there must be something, which can make changes in this perception. Anyhow, there are certain ways are available for the prevention of the damage in the process of treatment. The Treatment process would have the attributes that can make changes in the medication. The new medication would not damage the DNA in the process of treatment hopefully. It is mandatory to realize the importance in the changing of medication and produce such medication that can repair damage in this particular matter and factor. One can understand now the importance of the damage repair of DNA (Rueff & Rodrigues, 2016). 

Inhibition of Cell Death

It is quite imperative to understand that Inhibition of Cell Death is the major issue and way to treat the disease of cancer. One can understand that cell death has become a major issue for the patients who are suffering from cancer. The major cause is the non-effectiveness of the medications, which has been used in the process of cancer treatment. Therefore, it is very imperative to acknowledge the process of Inhibition of Cell Death for the better results ultimately.  One thing is very necessary to remember that Inhibition of Cell Death is the way to investigate the right medical process for the treatment (Foo & Michor, 2014).

On the other hand, one can understand that cells perform the great role in the recovery of the patients from major diseases like cancer and HIV as well.  Therefore, the physicians and doctors need to focus on the process of Inhibition of Cell Death.  In addition, it is necessary for the researcher to understand and acknowledge the factor that cell death could cause major infection and disease in the body of human beings ultimately.  It is obvious and proved that Inhibition of Cell Death is the major issue to focus and decrease the rate of deaths due to cancer (Liu, 2009). 

EMT & Metastasis

It is another issue to focus in the discussion about prevention from cancer. In addition, it is quite important to resolve the associated issues like development of cancers drugs.  It is the main issue of discussion in the paper and one can understand the significance of this issue in the medical history. According to medical reports, there are biggest institutions working to resolve the issue of drugs in cancer treatment. In the same way, the EMT and Metastasis are the major attributes and significant matters. The medical researchers and physicians need to overview this issue like the other significant issues of the death of cells and others (Okon, 2016). 

On the other hand, it is the fact that cancer is the major disease and people need to get more awareness for the better and healthy future. For this kind purpose, the researchers should come forward in order to reduce the rate of cancer in the future. The EMT and Metastasis are the main issues to handle in the prevention of negative effects of drugs of cancer. Therefore, it became very important to resolve the matters that are making things difficult in handling the cancer issues. It will cure the issues of drug development ultimately (Sameen, 2015). 

Heterogeneity of Cancer Cell

The cancer cell is located under the cancer stem cell and the Heterogeneity of Cancer Cell is quite an important issue in the development of cancer prevention drugs. The Heterogeneity of Cancer Cell can describe into two section or models and one is cancer stem cell.  It is very imperative to understand that Heterogeneity is mandatory for the noble cause of the researchers and physicians.  One can understand that medical research about the development of cancer drugs is in the process and everybody is putting a part in the efforts against the disease of cancer.  In the same way, the above-mentioned issue needs to be resolved on urgent basis (Chen, 2014).    

It will ultimately make things better for the human beings. These types of the issue have been the major part of the study in the process. This is why it became necessary for medical institutions to resolve the matter on the latest medical approaches and consequences. Otherwise, the level of growth would be negative and people could suffer more in the drugs of cancer.  Therefore, the development is essential and sustainable countries are making progress in this particular section. One can observe that the diseases rate is gradually declining and major diseases as if cancer has less impact on the healthy societies.  Now, it is obvious to resolve the matter of Heterogeneity of Cancer Cell (Okon, 2016). 

Conclusions

From the above discussion we can conclude that epigenetic modifications have a major role to play when it comes to development of resistance within the cancer cells. Resistance to drugs is a phenomenon that is present within the disease cells when therapies and treatments and these have no influence disease cells. Hence there are numerous techniques and methods that have been developed to cure the cancerous cells. These treatments are used to cure the cancer cells and halt their further growth and development which is very helpful in the disease relapse as well. Further research and development should be conducted in order to prevent the growth of the cells which will help the experts to cure the disease.

References   

Ahmad, A. (2014). Breast Cancer Metastasis and Drug Resistance: Progress and Prospects. Springer New York.

Akhdar, H., Legendre, C., Aninat, C., & Morel, F. (2012). Anticancer Drug Metabolism: Chemotherapy Resistance and New Therapeutic Approaches. In H. Akhdar, C. Legendre, C. Aninat, & F. Morel, Topics on Drug Metabolism (pp. 137-170). Intech.

Chen, J. (2014). Reactive Oxygen Species and Drug Resistance in Cancer Chemotherapy. Austin Journal of Clinical Pathology, 1(4), 1-7.

Dinsa, H., & Melesie, G. (2014). A Literature Review on Cancer Multi Drug Resistance and Its Therapy. International Journal of Pharma Sciences, 4(1), 417-423.

Eid, S. Y., El-Readi, M. Z., Fatani, S. H., Eldin, E. E., & Wink, M. (2015). Natural Products Modulate the Multifactorial Multidrug Resistance of Cancer. Pharmacology & Pharmacy, 6, 146-176.

Foo, J., & Michor, F. (2014). Evolution of acquired resistance to anti-cancer therapy. Journal of Theoretical Biology, 355, 10-20.

Housman, G., Byle, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., & Sarkar, S. (2014). Drug Resistance in Cancer: An Overview. Cancers, 6, 1769-1792.

Hu, T., Li, Z., Gao, C.-Y., & Cho, C. H. (2016). Mechanisms of drug resistance in colon cancer and its therapeutic strategies. World Journal of Gastroenterology, 22(30), 6876-6889.

Koushik, Rao, Kumar, & Karthikeyan. (2016). Nano Drug Delivery Systems to Overcome Cancer Drug Resistance – A Review. Journal of Nanomedicine & Nanotechnology, 7(3), 1-9.

Liu, F.-S. (2009). Mechanisms of Chemothrapeutic Drug Resistance in Cancer Therapy – A Quick Review. Taiwan J Obstet Gynecol, 48(3), 239-244.

Okon, I. (2016). The Paradox of Ant-cancer Agents and Recurring Emergence of Drug Resistance. Journal of Biomedical Sciences, 4(1:4), 1-4.

Rueff, J., & Rodrigues, A. S. (2016). Cancer Drug Resistance: Overviews and Methods. Springer New York.

Sameen, S. (2015). Hybrid Modeling of Cancer Drug Resistance Mechanisms. Universita di Pisa.

Sebens, S., & Schäfer, H. (2012). The Tumor Stroma as Mediator of Drug Resistance – A Potential Target to Improve Cancer Therapy? Current Pharmaceutical Biotechnology, 13, 1-14.

Ullah, M. F. (2008). Cancer Multidrug Resistance (MDR): A Major Impediment to Effective Chemotherapy. Asian Pacific Journal of Cancer Prevention, 9, 1-6.

Wang, H. (2015). Molecualr Mechanisms of Therapeutic Resistance in Cancer. University of Michigan.

Zahreddine, H., & Borden, K. L. (2013). Mechanisms and insights into drug resistance in cancer. Frontiers in Pharmacology, 4, 1-8.

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