The Development of Cancer Problem: 1998-2008 - Article Example

The Development of Cancer Problem: 1998-2008 Introduction The global occurrence of cancer makes it a major health concern that has cleaved millions of dollars for research. The ailment is equally common in modern and in developing countries which suggests that the discrepancies in the health care system is not an important factor for a substantial conclusion of its occurrence. This paper will highlight the significant breakthroughs of cancer research and its implications worldwide in terms of health care policy making and the creation of general health care standard. First is a discussion on the discovery that the cancer can be entirely caused by a virus which is contrary to the initial theory that molecular aberrations or genetic defects are the main rationale for the uncontrolled cell proliferation characteristics of cancer. HPV (human papillomavirus) is the first virus documented in 1999 to be the main reason for cervical cancer worldwide. The next part of the paper is the attempt of scientists, medical practitioners and researchers to cure cancer other tan resorting to chemotherapy and other invasive cancer treatments. A breakthrough in this field is the discovery of potent protein, angiostatin that works by cutting off the blood vessels formed by the tumour or cancerous cells, in order to provide itself with the right amount of nutrients to survive. However, success in this area is limited when it was soon found out that cells revert back after several waves of treatment because of resistance development by the genetically sound cancer cells. This is solved by the discovery of endostatin, a collegoud protein which is more potent than angiostatin and further prevents resistance by the cancer cells. Endostatin and angiostatin proved to be highly effective methods of controlling tumour growth, but, it is not specific on its target and therefore posing threats to other healthy cells in cancer patients. This dilemma is solved with the breakthrough came to be known as targeted molecular therapy. As the name suggests, this method of cancer prevention lies in its ability of targeting the exact molecular aberration responsible for cancer without effects to other cells. As a consequence, once the source of cancer is determined at the molecular level, drugs against cancer could be developed solely to target that defect. Years of cancer research further revealed that a very limited kind of cancer cells are able to reproduce an exact copy of its original self through a process called self-renewal. These cells have the capabilities exhibited by stem cells to transform into any kind of cells present in the tumour. This foundation changed the course of cancer research and currently, cancer therapy investigations are focused on targeting the cancer “stem cell” so to speak. Cancer as a virus The second most common cancer in the world is cervical cancer; the prevalence of such encouraged researchers and scientists to look into its aetiology and to determine its cause. In a study in 1999 published in the Journal of Pathology, it was found out that the main cause of cervical cancer worldwide is the human papillomavirus (HPV) (Walboomers, et. al. 1999). Samples of invasive cervical cancer were collected from 22 countries all over the world in order to establish a worldwide occurrence of the disease. This episode of HPV in cervical cancer is the first tumour shown to have been virally linked. The establishment of this link would mean that the elimination of this virus would also clear up the cases of cervical cancer all over the world and prophylactic vaccination might proved to be a successful method. The ramifications of this discovery are significant. Cervical cancer can be “prevented” rather than treated using non-invasive methods and therefore cost efficient. Further study of the behaviour of the virus would identify the women who are most likely to be at risk of this cancer. On the other hand, it was not instituted in the study whether all cervical cancer is caused by HPV and this proves the significance of the research (Walboomers, et. al. 1999). Cancer research, prevention, control and cure The development of angiostatin and endostatin paved way for the creation of a drug that works on any kind of cancer without developing resistance to it. The discovery of this new drug is the effects of the more than 30 years of laboratory and clinical research works of Dr. Michael O'Reilly and his team at Dr. Judah Folkman's laboratory in Children's Hospital based on the working premise that since cancer cannot grow without a steady supply of blood, once they block the tumour’s blood supply, then it dies (O’Reilly, et. al. 1997). The process of creating new blood vessels that supply blood that carries with it food and nutrients to the developing cancer tumour is called angiogenesis. When angiogenesis was detected as the main reason not only for cancer development but as a means for sustenance, researchers envisioned an anti-angiogenesis drug that will serve as a framework for cancer treatment (O’Reilly, et. al. 1997). This anti-angiogenesis drug will be designed to have the capacity to stop the process of blood vessel formation. However the earliest prototypes of these drugs did do well in slowing down the growth of the tumour but failed in entirely eradicate the metastases. The metastases are satellite cancer tumours that may not be visible to the naked eye or can even go as small as microscopic. Because they can be excessively minute, it is almost impossible for them to be detected especially under a very unsuspecting condition. This threat is even furthered, when these satellite tumours are scattered all over the body. A breakthrough in cancer drug research came in when the significance of the metastases was revealed. It has been an enigma for doctors why despite the removal of the satellite tumour, a few months later whole new metastases will appear and will eventually kill the patient (O’Reilly, et. al. 1997; Kolata, 1998). These anti-angiogenesis or genesis-inhibiting drugs often work by targeting the chemical signals that controls the vessel-making cells to stop forming blood vessels for them. However, resistance is developed by switching to other chemical signals and pathway and thus, vessel formation continues. Many cancer drugs are initially effective until capillaries that seem to have disappeared started to form again. These drugs attack the capillaries heedless that since these fast-growing tumours are also regular, genetically constant and therefore are equally capable of developing resistance to any drug treatment (O’Reilly, et. al. 1997). However, the Boston team of these cancer drug research at Children’s Hospital isolated a new protein that does not only inhibit the growth of capillaries and have shrunk the tumour has also prevented its regrowth after repeated treatment to the same protein. Endostatin, a more potent protein than angiostatin (which was distilled by Dr. O’Reilly from mice urine in 1994) is capable of shrinking a tumour in laboratory mice to microscopic size. The effectiveness of endostatin comes from its ability of singling out vessel-making cells and kills them off and does not merely impede the growth of tumours (O’Reilly, et. al. 1997). Figure 1. Specific Inhibition of Capillary Endothelial Cell Proliferation by Native and Recombinant Endostatin (O’Reilly, et. al. 1997) After the discovery of this protein that is capillary-specific; the next goal is to find out how to prevent the development of resistance of these tumours. To address such inquiry, the Boston team injected a specific amount of endostatin to mice in a “stop-and-start” method that triggers resistance. It was observed that initially the tumours shrunk since their capillaries and blood vessels were cut off; however, these vessels were re-formed when the treatment of endostatin ceased. This confirmed that tumours do develop resistance to endostatin. Dr. Folkman observed other significant findings; when these capillaries ceased to supply blood to the tumours, they went back to their inactive stage which is too small to see with an unaided eye until they do not grow back again within the lifetime of the mice. Dr. Folkman graphed the growing and the regression of these tumours till they became dormant (O’Reilly, et. al. 1997; Wade, 1997). Targeted molecular therapy A deeper understanding of cancer genesis led to the development of new drugs and on the improvement of the existing once. Along with the discovery that tyrosine kinase is able to activate signals that would result to uncontrolled and uninhibited cell division, another prospect of cancer prevention works on the premise of shutting off tyrosine kinase activity. A drug was developed in 2001 with the chemical compound number STI-571 that successfully prevents activities of tyrosine kinase (Druker, et. al. 2001). The action of tyrosine kinase is a molecular aberration that signals cells to divide unceasingly; this suggests therefore that STI-571 could also work for other types of cancers goes to the same pathway. Several testing on the drugs were made to patients with gastrointestinal stromal tumours, to adults and children with gliomas (a form of brain tumour), also tested to those with cancers on the connective tissue of sarcoma; to those with leukaemia and lymphomas and to those with breast, lungs and prostates cancers (Okie, 2001; Druker, et. al. 2001). The compound, STI-571, commonly called Gleevec proved to be effective for the treatment of leukaemia with the same favourable results to a kind of rare kind of stomach tumour. Clinical results have shown that STI-571 is a potent cancer treatment to those with chronic myelogenous leukaemia (CML), one of the most occurring forms of leukaemia that affects an estimated 5,000 people in the United States a year. The traditional method of treating patients with leukaemia is through bone marrow transplant. This method is highly dangerous because of the employment of an interferon that can potentially severely damage a patient. A direction of cancer drug research aims at the development of drug that spares the patient all the superfluous physical damage caused by conventional cancer treatment such bone marrow transplant and chemotherapies. Patients treated with STI-571 were able to regress to their normal blood count without significant clinical side effects unlike those seen after bone marrow transplant. Documented side effects of the compound are muscle cramps; nausea, diarrhea and fluid retention were observed to the patients. Moreover, fatigue, bleeding and an elevated level of liver enzymes where also recorded from the patients. However, these promising results of STI-571is still pressed with another predicament. For one, this compound has yet to pass an acid test which will determine that a patient will indeed love longer after treatment of the drug. The scientists acknowledge that there is no tangible proof that the drug will be able to extend the life of the cancer patient (Druker, et. al. 2001; Wade (b), 2001). The scientist and researchers of STI-571 is optimistic of its development. Traditional cancer drugs such as the protein endostatin and angiostatin works by targeting the blood vessel forming cells of the any kind of cancer tumour and thus killing it in the process, STI-571 is the first cancer drug that aims at the specific molecule that causes cancer, in this case, the tyrosine kinase molecule. In this line of analogy, it is predicted that more tailored drugs will be developed if these molecular abnormalities will be discovered. A new wave of cancer prevention through “targeted molecular therapy” was paved open with the advancement of STI-571, which is highly specific on the type of cell to target (Okie, 2001; Friend, 2001; Druker, et. al. 2001) Discovering specific cancer cells at the molecular level Targeted molecular therapy could be the Achilles’ heel of cancer and has started vigorous researches on the discovery of specific molecules that directly causes uncontrolled cell proliferations. These endeavours led scientist to identify cancer cells that are able to spread and deemed them as the most dangerous type. There are only few of these types of cancer cells that are able to spread and in 2003, the only type identified to have this ability are breast cancer cells. In a paper published in the Proceedings of the National Academy of Sciences entitled Prospective identification of tumorigenic breast cancer cells, breast cancer cells have the ability similar to those observed in stem cells, that is, they are able to grow into various kinds of cells. These breast cancer cells are able to make their own self copies, a process Dr. Michael Clarke, the study director, termed as self-renewal. Self-renewal capabilities mean that if one cell was unsuccessfully removed during the treatment, it is able to replicate itself and “produce all the other kinds of cells in the original tumor”. The ramifications of the phenomenon of self-renewal of cancer cells are another quandary in cancer and cancer drug research. Notwithstanding this dangerous and threatening discovery about cancer cells self-renewal capabilities, in the light of targeted molecular therapy; this is the best chance to discovery more ways that will target specific molecules responsible for such phenomenon (Muhammad, et. al. 2003). The discovery of breast cancer cells self-renewal capabilities: a novel course in cancer drug research Specific cells, identified through the protein patterns in their surface membranes, were isolated and injected into mice and made to develop into tumours. It was observed the fresh tumours that grew were of the same cellular make-up to the ones originally injected. The same simulation methods and researched were previously done to other kinds of cells gathered from other cancer cells, but was unsuccessful to copying the original. This led researchers and scientists to conclude why cancer drugs do not seem to work well on breast cancer cells and possibly to other cells yet to be accounted exhibiting the same characteristics (Muhammad, et. al. 2003). In the words of Dr. Max Wicha, “If we are to have any real cures in advanced breast cancer, it will be absolutely necessary to eliminate these cells”; “these cells” referred here are those types of cells which has the capacity to make copies of themselves and are able to replicate “all” the other kinds of cells in the satellite tumour. They are similar to the body’s key cells, which after being triggered by definite hormones and signals transform into the cell they are ought to become. Comparable and analogous cells with the same characteristics have been recorded in leukaemia, although these ones in breast cancer cells are the first ones found in tumours (Muhammad, et. al. 2003). With this advancement in cancer cell research, doctors and scientist was directed to a new path on cancer therapies and drugs development. The self-renewal capabilities suggest that therapy models scientists have as a mantra since the development of STI-571 which targets specific molecules could be mistaken for they may be “have been targeting the wrong cells with the wrong treatments”, according to Dr. Max Wicha. A new prospect opened in cancer drug research and that is the improvement of drugs that are stem cell specific (Breast cancer danger cells found). Stem cell specific cancer drug research For the reason of the discovery of the capabilities of these stem cells, many researchers have turned their direction into the finding of the specific stem cells that could be responsible for the development of other types of cancer. In order to create therapies that kill stem cells, they have to be first identified and assayed accordingly. In a report made by Dr. Elaine Vickers, of Cancer Research UK, she stated announced that 22% of the reported cases of cancer have fallen, highly attributed to earlier detection and treatment. She hopefully pointed out that the discovery of these stem cells could spell treatment for breast cancer. This research is deemed to flourish into the possible classification of those aggressive cells that will decide on whether cancer will spread or not (Breast cancer danger cells found). References Druker, B., Talpaz, M., Resta, D., Peng, B., Buchdunger, E., Ford, J., Lydon, N., Kantarjian, H., Capdeville, R., Ohno-Jones, S., & Sawyers, Charles. (2001). Efficacy and safety of a specific inhinitor of the BCR_ABL tyrosine kinase in chronic myeloid leukemia. The New England Journal of Medicine. 344.14, pp. 1031-1037. Friend, T. (2001). 'Wave of future' cancer pill OK'd Targets bad cells, reduces many of the side effects. USA Today. Kolata, G. (1998). Hope in the lab: a special report.; a Cautious Awe Greets Drugs That Eradicate Tumors in Mice. The New York Times. Okie, S. (2001). Cancer Drug Approved Quickly; Gleevec Dramatically Effective Against a Type of Leukemia. The Washington Post. O’Reilly, M., Boehm, T., Yuen, S., Fukai, N., Vasios, G., Lane, W., Flynn, E., Birkhead, J., Olsen, B., & Folkman, J. (1997). Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. Vol. 88, 277–285. Muhammad, A., Wicha, M., Benito-Hernandez, A., Morrison, J., Clarke, M. (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences. 100.7, 3983–3988. Wade, N. (1997). Tests on Mice Block a Defense by Cancer. The New York Times Wade, N. (2001). Powerful Anti-Cancer Drug Emerges from Basic Biology. The New York Times. Walboomers, J., Jacobs, M., Manos, M., Bosch, F.X., Kummer, A., Shah, K., Snijders, P., Peto, J., Meijier, C., & Munoz, Nubia. (1999). Human Papillomavirus is a necessary cause of invasive cervical cancer worldwide. Journal of Pathology. 189. pp. 12–19 Read More