Scientific Development in Cancer Patients - Term Paper Example

? Scientific Development in Cancer Patients - Scientific Development in Cancer Patients Introduction: Cancer is among the leading causes of death worldwide. It is a devastating disease, not only because of associated high mortality rates but also because it severely affects the quality of life of the patient. Age is one of the most important risk factor associated with this disease. Therefore, the incidences are increasing steadily as improvement in the health care facilities has raised the average life expectancy mostly in the developed countries. Cancer is a chronic disease and most of the victims experience a painful death. The treatment is mostly aimed at increasing the life expectancy of the patient and five year survival rate is considered a success in most of the cases. In the human body any cell can become malignant. So identifying the type of cancer, the cell from which it originates, is crucial in devising a management plan and initiating appropriate treatment for the patient. Moreover, some malignancies tend to spread more rapidly than the others. Hence, an evaluation is required to determine whether a risky but more aggressive approach is required in management. Lot of work is underway to devise better treatment options for cancer patients. Over the past decade research has opened new doors in the field of cancer management. These efforts are reinforced by researches in other fields aimed to understand the basic mechanism of how malignant cells overcome the inbuilt defense system that restrict abnormal growth. By understanding these particular changes that occur in a malignant cell we can develop drugs that can prevent these transitions. This paper aims to provide a brief review of the scientific developments that have revolutionized or shaped the treatment for cancer patients over the past few decades. Traditional Treatments: Traditionally, cancer management mainly consisted of surgery alone. As the field of science developed over the period of time new treatment options were introduced. With the progress in the field of radiology useful applications of radiations were invented. Since then radiation therapy has served well as an adjunct to the surgical excision of the tumor. With the advancement in the field of biochemistry, newer lab techniques enabled the production of drugs that were capable of destroying the malignant cells. Unfortunately these drugs had various side effects and were not very specific in targeting the desired cells. Despite this fact chemotherapy has been a backbone in the cancer treatment over the past few decades. So radiation and chemotherapy along with surgery remained the key options for the management of cancer patients.1 Recent Scientific Developments: The recent scientific developments can be divided into two categorize for descriptive purposes. First category comprises of those advancements that have introduced improvements in the already existing cancer managements and the other category includes those new breakthroughs that have promised to revolutionize the cancer treatment in the upcoming future. So the recent developments had further added more sophisticated techniques in the traditional treatments. For example, newer drugs have been developed that are more specific for the tumor cell antigens and produce fewer adverse effects. Introduction of external beam therapy and proton therapy for cancer has reinforced the radiation therapy. Similarly, the newer techniques in surgery promise more success and fewer chances of recurrences in the cancer patient. Apart from the improved existing treatments that targets tumor cells directly; the latest drugs such as angiogenesis and tumor growth inhibitors target the factors that help the tumor to grow.2 Angiogenesis and Tumor growth Inhibition: As discussed earlier, angiogenesis is essential for the growth of any solid tumor as it provides the essential ingredients required to keep the malignant cells alive. Therefore, one newer strategy in combating the cancer is to inhibit the formation of these new blood vessels. This will not only prevents the abnormal growth but will also limit the metastasis of cancer cells from the origin to other part of the body. From the previous researches it has been confirmed that tumor cells produce various angiogenic factors that stimulate the growth of new blood vessels. These factors include vascular endothelial cell growth factor (VEGF), vascular permeability factor (VPF) and fibroblast growth factors (FGF). Interestingly, some cancer cells also produce angiogenic inhibitors. Formation of new blood vessels is normally balanced by these two opposite regulators. Initially, angiostatin was the only angiogenesis inhibitor known to us that specifically inhibit the endothelial cell proliferation. But with the scientific development in the field of cancer treatment newer angiogenesis inhibitors have been identified such as interferon-alpha, platelet factor 4 and interferon-inducible protein 10.3 Angiostatin, however, is the most studied angiogenesis inhibitor. It has been proved that its secretion from the primary tumors can effectively inhibit their angiogenesis and metastasis. Further experiments showed that a systemic therapy with angiostatin can remarkably halt the growth of tumor cell by bringing a balance between apoptosis and proliferation of tumor cells. This was a breakthrough discovery that is currently being used to treat cancer patients around the world. Its effectiveness is still being tested and a hunt for newer similar agents is on the rise. One of the most significant attribute of this medication is that no tumor has shown resistance to the therapy and no toxicity has been observed at the tested dose of up to 100mg/kg.4 Endostatin: Hard work by many dedicated scientist fruited a major breakthrough when they successfully isolated a new type of angiogenesis inhibitor in the form of Endostatin. A murine hemangioendothelioma cell line (EOMA) was observed for any evidence of angiogenesis inhibitor production. From the previous data it was evident that introduction of already isolated inhibitors cause inhibition of endothelial cell proliferation in vitro. So based on this knowledge, a conditioned media from EOMA cell line was added to the capillary endothelial cells stimulated with fibroblast growth factor. During the 72 hours proliferative assay, the conditioned media from the EOMA effectively inhibited the proliferation of capillary endothelial cells. Therefore, it was confirmed that there are certain inhibitors in conditioned media but the exact nature was not known. The other factors were kept constant during the experiment and it was ensured that this inhibition was not due to angiostatin activity. Further, the structure of this inhibitor was identified and was traced to a collagen XVIII fragment. After confirmation that the founded structure matched the purified 20 kDa protein present in the EOMA conditioned media, this fragment was named as Endostatin. In the experimental mice endostatin has proved to be more potent than the angiostatin. It has shown the ability to regress the tumor and keeps it dormant. This scientific development can prove to be a major breakthrough in developing a potent drug for the treatment of cancer. It also highlights the need to think tumor as two distinct components. One is the tumor cells that proliferate and give rise to the tumor mass. Angiogenesis is the other component and both these component helps in the development of the other. Therefore, the treatment should not only target the cancer cells or angiogenesis alone. A therapy that takes care of both these components will be optimum in treating the cancer. Therefore, chemotherapy combined with an angiogenesis inhibitor can prove to be a better at killing the cancer than any of these therapies alone.5 Prospective Identification: Breast cancer is the most common cause of cancer related deaths in women worldwide. Despite widespread breast cancer awareness campaign its incidence is on the rise. The current therapies have proved ineffective due to emergence of therapy resistance cancer cells. Therefore, development of a new strategic management plan is required to overcome this hurdle. The new scientific advancement in the field of cell recognition using certain markers has led to a unique theory. It has been hypothesized that in a tumor mass only a small proportion of the cells has the capability to exhibit property of malignant and cancerous growth. This has been previously tested for acute myelogenous leukemia in mice where few identical cells with similar markers were able to produce malignant clones whereas the other cells did not exhibit reproduction abilities. But for solid tumor such conclusive evidences are not available. If it can be concluded that this hypothesis also apply for solid tumors such as breast cancer than those specific cells can be targeted for treatment. Moreover, if the survivor abilities of only these few cells can be identified than that information can be used to develop therapeutic strategies. So an experiment was designed, similar to the one used for acute myelogenous leukemia, in which mice were implanted with breast tumor specimens. These specimens were taken from human breast tumors within an hour after surgery and were sliced to produce a 2x2 mm pieces. These pieces were then implanted on the both mammary fat pads of the mice and were observed for tumor growth. After tumor growth was evident samples were taken for marker analysis. The results obtained from this experimentation were very encouraging. The prospective identification of tumor cells from 8 out of 9 patients had showed that they were from CD44+CD24-lowLineage. A very small number of cells with this particular phenotype were able to produce tumor in mice whereas huge number of cells with other phenotypes failed to develop any malignancy. This concludes some very important findings. When these particular phenotypic cells divide and produce new cells either the same lineage with similar phenotype is produced capable of further division or some other phenotype is produced which just add up to the bulk but actually are not the cancerous cells. This partially explains why during chemotherapy tumor regress but relapse is very common. Actually these particular cells with the capability to reproduce are more resistance to the chemotherapy as they have more weapons to combat the anticancer drugs. These cells have increased expression of BCL-2 family proteins on their cell surface as well as increased number of membrane transporters that resist most cancer drugs. So they are actually not affected by the therapy. That is why mostly the other “non-cancerous” cells are affected by the anticancer drugs reducing the tumor size and giving an impression of regression. The fewer but most important cells survive and are responsible for relapse in the future. Therefore, this discovery can spot light the research on these cells and encourage more experiments to be conducted involving other malignant tissues so that a more effective treatment can be developed for cancer patients.6 Tyrosine Kinase Inhibition: Chronic Myeloid Leukemia (CML) is a cancer that involves the white blood or myeloid cells. It is characterized by abnormal proliferation or cloning of myeloid lineage in the bone marrow. The disease has three main phases; chronic phase, accelerated phase and blast crisis. Logically more white cells should mean more immunity. But this is not the case as these abnormally formed cells do not undergo proper differentiation therefore they cannot perform their function properly. In fact, they hinder the activities of other normal white blood cells and limit their production decreasing the overall immunity of the victim and making them more susceptible to infections. The current treatment options for this cancer include allogenic bone marrow transplantation and drug therapy with interferon alpha. Both of these therapies have their drawbacks. Interferon alpha has many associated adverse effects although it has shown to prolong the overall survival rates in CML patients. The allogenic bone marrow transplantation is the only effective treatment but it is also associated with substantial morbidity and mortality. Moreover, it is not easy to find a suitable donor for the allogenic transplantation.7 The reciprocal translocation of the long arms between chromosome 9 and 22 results in the generation of the fusion protein known as BCR-ABL which is a constitutively activated tyrosine kinase. This tyrosine activity is believed to be responsible for the uncontrolled proliferation of the myeloid cells. Therefore, the inhibition of tyrosine kinase can prove to be an effective treatment for chronic myeloid leukemia. A research study was conducted to determine the affectivity of STI571, a tyrosine kinase inhibitor, in treating CML. During the trials this drug was administered to 83 patients orally suffering from CML. These patients had failed to respond to interferon alpha and were in the chronic phase of the disease. The dose of STI571 ranged from 25 to 1000 mg per day. The data collected after four weeks of therapy concluded very encouraging results. Most of the patients treated with the tyrosine kinase inhibitor demonstrated hematological and cytogenetic effects. Most importantly drug was well tolerated by the patients and there were no significant side effects apart from mild nausea, edema, myalgia and diarrhea. So the study showed that tyrosine kinase inhibitor can be very effective in the treatment of CML patients especially those not responding to the interferon alpha. This is a relatively new development but it promises a good potential for the development of more potent anticancer drugs for the treatment of chronic myeloid leukemia.8 Prevalence of HPV and Cervical Cancer: The latest development in identifying the underlying pathological causes of cancer has led to improved treatment strategies over the past decades. Cervical cancer is the second most common cancer in women and affects millions around the world. It is believed that human papillomavirus is the root cause in a very high percentage of the cases. A recent study however showed that this association of HPV in the development of cervical cancer is lot more than previously concluded. It was proposed that the present testing for HPV in the cervical cancer patients has produced many false negative results. Therefore, in this study previously negative patients were reanalyzed using HPV serum antibodies and HPV DNA. The data showed that most of these patients previously identified as HPV negative by using PCR were positive for HPV DNA. This gives way to the understanding that HPV is the underlying cause for about 99.7% cases of cervical cancer. The finding also has an application from the management prospective. It implies that if appropriate vaccination plan is initiated that can reduce the number of women affected by the HPV infection cervical cancer can be virtually eliminated from the world.9 Conclusion: After this walk through in the timeline of scientific development for the cancer treatments, certain points can be concluded. Over the past decade the advancement in the field of science has led to important discoveries that shows promising potential in developing more effective treatments for cancer patients. The latest techniques offer diverse ways of producing anticancer drugs that are more potent and more specific in their role of targeting the cancer cells. This development in the field of cancer treatment is highly reinforced by researches that try to understand the exact mechanisms in the formation of malignant tumors. References: Al-Hajj, Muhammad, Wicha, Max S., Benito-Hernandez, Adalberto, Morrison, Sean J., and Clarke, Michael F. n.d. Prospective identification of tumorigenic breast cancer cells. The National Academy of Sciences. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=153034. Druker BJ, M Talpaz, DJ Resta, B Peng, E Buchdunger, JM Ford, NB Lydon, et al. 2001. "Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia". The New England Journal of Medicine. 344 (14): 1031-7. Nathan, David G. 2007. The cancer treatment revolution: how smart drugs and other new therapies are renewing our hope and changing the face of medicine. Hoboken, N.J.: John Wiley & Sons. O'Reilly MS, T Boehm, Y Shing, N Fukai, G Vasios, WS Lane, E Flynn, JR Birkhead, BR Olsen, and J Folkman. 1997. 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