Treatment of cancer/Volume I: An introduction to cancer treatments

In this volume we will summarize what cancer is, what are its causes, screening methods and different ways to treat different varieties of cancer.

Chapter I: What is cancer?

Cancer is the common name of a group of diseases in which normal cells are damaged and do not undergo programmed cell death as fast as they divide via mitosis. These abnormal cells growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. General symptoms of cancer are weight loss or tiredness. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. Currently has being identifying hundreds types of cancer, since each one is different they are treated in different ways.

History of cancer

The earliest known descriptions of cancer appear in several papyri from Ancient Egypt. The Edwin Smith Papyrus was written around 1600 BC (possibly a fragmentary copy of a text from 2500 BC) and contains a description of cancer, as well as a procedure to remove breast tumours by cauterization.

Hippocrates (ca. 460 BC – ca. 370 BC) described several kinds of cancer, referring to them by the term karkinos (carcinos), the Greek word for crab or crayfish, as well as carcinoma. This comes from the appearance of the cut surface of a solid malignant tumour, with "the veins stretched on all sides as the animal the crab has its feet, whence it derives its name". Since it was against Greek tradition to open the body, Hippocrates only described and made drawings of outwardly visible tumors on the skin, nose, and breasts. In the 2nd century AD, the Greek physician Galen used oncos (Greek for swelling) to describe all tumours, reserving Hippocrates' term carcinos for malignant tumours. Galen also used the suffix -oma to indicate cancerous lesions. It is from Galen's usage that we derive the modern word oncology.

With the widespread use of the microscope in the 18th century, it was discovered that the 'cancer poison' eventually spreads from the primary tumor through the lymph nodes to other sites ("metastasis"). This view of the disease was first formulated by the English surgeon Campbell De Morgan between 1871 and 1874.

The renowned Scottish surgeon Alexander Monro saw only 2 breast tumor patients out of 60 surviving surgery for two years. In the 19th century, asepsis improved surgical hygiene and as the survival statistics went up, surgical removal of the tumor became the primary treatment for cancer. With the exception of William Coley who in the late 19th century felt that the rate of cure after surgery had been higher before asepsis (and who injected bacteria into tumors with mixed results), cancer treatment became dependent on the individual art of the surgeon at removing a tumor.

In 1883 Edouard Van Beneden discovered a cell structure which was described by Theodor Boveri in 1888 and named centrosome. Bovere postulated that chromosomes were distinct and transmitted different inheritance factors and he suggested that mutations of the chromosomes could generate a cell with unlimited growth potential which could be passed on to its descendants.

The genetic basis of cancer was recognised by Bovery in 1902 Boveri, after reasoning that a malignant tumor begins with a single cell in which the makeup of its chromosomes becomes scrambled, causing the cells to divide uncontrollably. He proposed carcinogenesis was the result of aberrant mitoses and uncontrolled growth caused by radiation, physical or chemical insults or by microscopic pathogens, and also proposed the existence of cell cycle check points, tumor suppressor genes and oncogenes. Bovery discovered a method to generate cells with multiple copies of the centrosome, and speculated that cancers might be caused or promoted by radiation, physical or chemical insults or by pathogenic microorganisms.

When Marie Curie and Pierre Curie discovered radiation at the end of the 19th century, they stumbled upon the first effective non-surgical cancer treatment. With radiation also came the first signs of multi-disciplinary approaches to cancer treatment. The surgeon was no longer operating in isolation, but worked together with hospital radiologists to help patients.

In 1984, Harald zur Hausen discovered first HPV16 and then HPV18 responsible for approximately 70% of cervical cancers. For discovery that human papillomaviruses (HPV) cause human cancer, zur Hausen won a 2008 Nobel Prize.

Since 1971 the United States has invested over $200 billion on cancer research; that total includes money invested by public and private sectors and foundations. Despite this substantial investment, the country has seen just a five percent decrease in the cancer death rate (adjusting for size and age of the population) between 1950 and 2005.

Carcinogens

Carcinogen are substances, radionuclide, or radiation that promotes carcinogenesis, the formation of cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Carcinogens can be classified as genotoxic or nongenotoxic.

• Genotoxins cause irreversible genetic damage or mutations by binding to DNA. Genotoxins include chemical agents like N-nitroso-N-methylurea (NMU) or non-chemical agents such as ultraviolet light and ionizing radiation. Certain viruses can also act as carcinogens by interacting with DNA.

• Nongenotoxins do not directly affect DNA but act in other ways to promote growth. These include hormones and some organic compounds.[22]

Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke.

Classification of possible carcinogens

The International Agency for Research on Cancer (IARC) has published a series of Monographs on the Evaluation of Carcinogenic Risks to Humans that have been highly influential in the classification of possible carcinogens and grouped them in the following categories:

• Group 1: the agent (mixture) is definitely carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans.
• Group 2A: the agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans.
• Group 2B: the agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans.
• Group 3: the agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans.
• Group 4: the agent (mixture) is probably not carcinogenic to humans.

Procarcinogen is a precursor to a carcinogen. One example is nitrites when taken in by the diet. They are not carcinogenic themselves, but turn into nitrosamines in the body, which can be carcinogenic.

Examples of carcinogens

There are many natural carcinogens. Aflatoxin B1, which is produced by the fungus Aspergillus flavus growing on stored grains, nuts and peanut butter, is an example of a potent, naturally occurring microbial carcinogen. Certain viruses such as hepatitis B and human papilloma virus have been found to cause cancer in humans. The first one shown to cause cancer in animals is Rous sarcoma virus, discovered in 1910 by Peyton Rous. Other infectious organisms which cause cancer in humans include some bacteria (e.g. Helicobacter pylori) and helminths (e.g. Opisthorchis viverrini and Clonorchis sinensis.

Dioxins and dioxin-like compounds, benzene, kepone, EDB, and asbestos have all been classified as carcinogenic. As far back as the 1930s, Industrial smoke and tobacco smoke were identified as sources of dozens of carcinogens, including benzo[a]pyrene, tobacco-specific nitrosamines such as nitrosonornicotine, and reactive aldehydes such as formaldehyde, which is also a hazard in embalming and making plastics. Vinyl chloride, from which PVC is manufactured, is a carcinogen and thus a hazard in PVC production.

Glyphosate: A broad-spectrum systemic herbicide and crop desiccant. It was discovered to be an herbicide by Monsanto chemist John E. Franz in 1970. Monsanto brought it to market for agricultural use in 1974 under the trade name Roundup. In March 2015, the World Health Organization's International Agency for Research on Cancer (IARC) classified glyphosate as "probably carcinogenic in humans" (category 2A) based on epidemiological studies, animal studies, and in vitro studies. Monsanto adquired Bayer on June 7, 2018.

Chapter II: Cancer screening

Cancer screening aims to detect cancer before symptoms appear. This may involve blood tests, urine tests, DNA tests other tests, or biological imaging.

Biological imaging

Biological imaging may refer to any imaging technique used in biology, includes Medical imaging, Magnetic resonance imaging (MRI), Photoacoustic Imaging, Ultrasound imaging,

• Photoacoustic imaging (optoacoustic imaging) is a biomedical imaging modality based on the photoacoustic effect.

• Medical imaging: It is the technique and process of creating visual representations of the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology).

• Nuclear pharmacy, also known as radiopharmacy, involves preparation of radioactive materials for patient administration that will be used to diagnose and treat specific diseases in nuclear medicine. The concept of nuclear pharmacy was first described in 1960 by Captain William H. Briner while at the National Institutes of Health (NIH) in Bethesda, Maryland.

Scintimammography: Is a procedure where Women receive an injection of a small amount of a radioactive substance which is taken up by cancer cells, and a gamma camera is used to take pictures of the breasts. One of the markes used is Technetium-99 (99Tc), which is an isotope of technetium (Technetium is a chemical element with the symbol Tc and atomic number 43) discovered in 1938. It is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used medical radioisotope. It is a radioactive tracer and can be detected in the body by medical equipment (gamma cameras). In 1960 Powell Richards became the first to suggest the idea of using technetium as a medical tracer medical or scanning of Tc-99m applications.

Cancer genome sequencing

Cancer_genome_sequencing helps in determining which cancer the patient exactly has for determining the best therapy for the cancer.

Papanicolaou test

Is a method of cervical screening used to detect potentially precancerous and cancerous processes in the cervix (opening of the uterus or womb). Abnormal findings are often followed up by more sensitive diagnostic procedures and if warranted, interventions that aim to prevent progression to cervical cancer. The test was independently invented in the 1920s by Dr. Georgios Papanikolaou and Dr. Aurel Babeș and named after Papanikolaou. A simplified version of the test was introduced by Anna Marion Hilliard in 1957.

Chapter III Cure(s) of cancer

Because "cancer" refers to a class of diseases, it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases.[5] Angiogenesis inhibitors were once thought to have potential as a "silver bullet" treatment applicable to many types of cancer, but this has not been the case in practice.

Chapter IV: Treatments of cancer

Cancer can be treated by surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy (including immunotherapy such as monoclonal antibody therapy) and synthetic lethality.

The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status).

Complete removal of the cancer without damage to the rest of the body (that is, achieving cure with near-zero adverse effects) is the ideal goal of treatment and is often the goal in practice. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness; and chemotherapy and radiotherapy can have a negative effect on normal cells.[2] Therefore, cure with nonnegligible adverse effects may be accepted as a practical goal in some cases; and besides curative intent, practical goals of therapy can also include (1) suppressing the cancer to a subclinical state and maintaining that state for years of good quality of life (that is, treating the cancer as a chronic disease), and (2) palliative care without curative intent (for advanced-stage metastatic cancers).

• Surgery
• Radiation therapy
• Chemotherapy
• Targeted therapies
• Immunotherapy
• Hormonal therapy
• Angiogenesis inhibitors
• Synthetic lethality

Alternative cancer treatments for cancer that have not been approved by the government agencies responsible for the regulation of therapeutic goods. They include diet and exercise, chemicals, herbs, devices, and manual procedures. The treatments are not supported by evidence, either because no proper testing has been conducted, or because testing did not demonstrate statistically significant efficacy. Proton therapy

Experimental cancer treatment: Are non-medical therapies intended to treat cancer by improving on, supplementing or replacing conventional methods (surgery, chemotherapy, radiation, and immunotherapy). Experimental cancer treatments cannot make medical claims, since their efficacy in specif types of cancer and adverse effects have not being verified. These include the following:

• Bacterial Treatments
• Drug Therapies; HAMLET (human alpha-lactalbumin made lethal to tumor cells), Dichloroacetate Treatment, Quercetin Treatment, Insulin Potentiation therapy, p53 Activation Therapy, BI811283.
• Gene Therapy
• Epigenetic Options
• Telomerase Deactivation Therapy
• Radiation Therapies: Photodynamic Therapy, Hyperthermiatic Therapy.
• Cold Atmospheric Plasma Treatment
• Electromagnetic treatments

Chapter V: Antineoplastic Drugs

Chemotherapy applied to cancer is a therapy that uses one or more anti-cancer drugs (chemotherapeutic agents) as a form of cancer treatment or standardized chemotherapy regimen (a plan designed to give a positive result). Chemotherapy can also be applied for the treatment of others illness as it is sickle cell, among others. These chapter is reviewed extensively in the Volume II of this book.

Chapter VI Current research

Diverse laboratories are developing new drugs and that are in early stage of research or are in clinical trials while their efficacy and safety is studied.

Glossary

Antineoplastic drug: Are medications used to treat cancer. Antineoplastic drugs are also called anticancer, chemotherapy, chemo, cytotoxic, or hazardous drugs. T

Cure: Is a substance or procedure that ends a medical condition, such as a medication, a surgical operation, a change in lifestyle or even a philosophical mindset that helps end a person's sufferings; or the state of being healed, or cured. Many diseases can be cured, when this can be achieved, the symptoms and state of the illness is completely eliminated from the patient or host of the illness. The most common example of a complete cure is a bacterial infection treated with antibiotics. Patients could respond different to medical treatments, being cured or not when receiving the same treatment. Cure fraction or cure rate, is determined by comparing disease-free survival of treated people against a matched control group that never had the disease.

Incurable diseases: A disease is said to be incurable with current medical technologies when there is a chance of the patient relapsing, no matter how long the patient has been in remission. Current research in medicine aim to cure what we know now as incurable diseases. Treatment of incurable diseases allow to manage them using therapies, surgery, and other treatments in order to lessen the symptoms and effects of the illnesses. Neoplasm: a type of abnormal and excessive growth, called neoplasia, of tissue. Can be caused by an abnormal proliferation of tissues, which can be caused by genetic mutations. Not all types of neoplasms cause a tumorous overgrowth of tissue.

Macrophages (Greek: big eaters, from Greek μακρός (makrós) = large, φαγεῖν (phagein) = to eat) are a type of white blood cell, of the immune system, that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface in a process called phagocytosis.

Oncovirus: Are a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin. It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus". The vast majority of human and animal viruses do not cause cancer, probably because of longstanding co-evolution between the virus and its host. Oncoviruses have been important not only in epidemiology, but also in investigations of cell cycle control mechanisms such as the retinoblastoma protein.

Recrudescence; Is the revival of material or behavior that had previously been stabilized, settled, or diminished. In medicine, it is usually defined as the recurrence of symptoms after a period of remission or quiescence, in which sense it can sometimes be synonymous with relapse. In a narrower sense it can also be such a recurrence with higher severity than before the remission.

Relapse: Is a recurrence of a past (typically medical) condition. It is also called recidivism. multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or recrudescence.

Response: is a partial reduction in symptoms after treatment.

Recovery: Is a restoration of health or functioning. A person who has been cured may not be fully recovered, and a person who has recovered may not be cured, as in the case of a person in a temporary remission or who is an asymptomatic carrier for an infectious disease.

Prevention: Is a way to avoid an injury, sickness, disability, or disease in the first place, and generally it will not help someone who is already ill (though there are exceptions).

Therapy: Is to treat a problem, and may or may not lead to its cure.

Tumor: (American English) or tumour (British English), Latin for swelling, one of the cardinal signs of inflammation, originally meant any form of swelling, neoplastic or not. Some neoplasms do not form a tumor; these include leukemia and most forms of carcinoma in situ. Tumor is also not synonymous with cancer. While cancer is by definition malignant, a tumor can be benign, precancerous, or malignant.

References

1. The Free Dictionary. Mosby's Medical Dictionary, 8th Edition. © 2009, Elsevier., 2009. Web. 28 Oct. 2012. http://medical-dictionary.thefreedictionary.com/compartment+model.

1. Dhillon, Soraya and Gill, Kiren. "Basic Pharmacokinetics." 28 Oct. 2012. http://www.pharmpress.com/files/docs/clinical_pharmacokinetics_samplechapter.pdf