Treatment of cancer/Printable version

Treatment of cancer

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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

Volume II: Antineoplastic drugs

Antineoplastic drugs are drugs that are used to eliminate patient's neoplastic processes. Neoplasms are types of abnormal and excessive growths, called neoplasia, of tissue, a word that is formed from Ancient Greek νέος- neo ("new") and πλάσμα plasma ("formation", "creation").

The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and it persists growing abnormally, even if the original trigger is removed. This abnormal growth usually (but not always) forms a mass. When it forms a mass, it may be called a tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology.

Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia.

A common group of antineoplastic drugs are cytostatic drugs, medicines that inhibits cell growth by cytostasis (cyto – cell; stasis – stoppage), or the inhibition of cell growth and multiplication. Cytostatic mechanisms and drugs generally occur together with cytotoxic ones. Cytostasis is an important prerequisite for structured multicellular organisms. Without regulation of cell growth and division only unorganized heaps of cells would be possible, other uses of cytostatic drugs are the treatment of skin diseases, treatment of infections and hygienic products. They slow down or stop the growth of specific cells by inhibiting their cell division. They work damaging the DNA of a cell, affecting cells cycle (mitosis) or disturbing the metabolism. Currently are under research many non cytotoxyc antineoplastic drugs.

I.- Drugs that damage cell’s DNA

Alkylating antineoplastic agents

Alkylating agents are used in cancer treatment attaching an alkyl group (CnH2n+1) to DNA. The alkyl group is attached to the guanine base of DNA, at the number 7 nitrogen atom of the purine ring. Since cancer cells, in general, proliferate faster and with less error-correcting than healthy cells, cancer cells are more sensitive to DNA damage—such as being alkylated. Alkylating agents are used to treat several cancers. However, they are also toxic to normal cells (cytotoxic), particularly cells that divide frequently, such as those in the gastrointestinal tract, bone marrow, testicles and ovaries, which can cause loss of fertility. Most of the alkylating agents are also carcinogenic.

Platinum-based antineoplastic

They are coordination complexes of platinum that work crosslinking of DNA as monoadduct, interstrand crosslinks, intrastrand crosslinks or DNA protein crosslinks. Mostly they act on the adjacent N-7 position of guanine, forming a 1, 2 intrastrand crosslink. The resultant crosslinking inhibits DNA repair and/or DNA synthesis in cancer cells. These drugs are used to treat almost half of people receiving chemotherapy for cancer. These drugs can cause a combination of more than 40 specific side effects which include neurotoxicity, which is manifested by peripheral neuropathies including polyneuropathy.

Antimetabolites

Antimetabolites are molecules that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid; thus, competitive inhibition can occur, and the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used as chemotherapy for cancer.

Topoisomerase inhibitor

are chemical compounds that block the action of topoisomerase (topoisomerase I and II), which is a type of enzyme that controls the changes in DNA structure by catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle.

It is thought that topoisomerase inhibitors block the ligation step of the cell cycle, generating single and double stranded breaks that harm the integrity of the genome. Introduction of these breaks subsequently leads to apoptosis and cell death. Topoisomerase inhibitors can also function as antibacterial agents. Quinolones (including nalidixic acid and ciprofloxacin) have this function.[4] Quinolones bind to these enzymes and prevent them from decatenation replicating DNA.

Enzymes

Enzimes are molecules that accelerate chemical reactions. Enzymes can be either anabolic or catabolic (can be used to form smaller molecules from a larger molecule or to do the opposite). The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products.

Asparaginase is an enzyme that is used as medication in the form of L-asparaginase is used to treat acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and non-Hodgkin's lymphoma.

The rationale behind asparaginase is that it takes advantage of the fact that acute lymphoblastic leukemia cells and some other suspected tumor cells are unable to synthesize the non-essential amino acid asparagine, whereas normal cells are able to make their own asparagine; thus leukemic cells require high amount of asparagine.[16] These leukemic cells depend on circulating asparagine. Asparaginase, however, catalyzes the conversion of L-asparagine to aspartic acid and ammonia. This deprives the leukemic cell of circulating asparagine, which leads to cell death.

II.- Drugs that act over cell mitosis without modifying cells DNA

Mitotic inhibitor are drugs that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow and eventually spread through the body (metastasize) through continuous mitotic division. Thus, cancer cells are more sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are also used in cytogenetics (the study of chromosomes), where they stop cell division at a stage where chromosomes can be easily examined.

Mitotic inhibitors are derived from natural substances such as plant alkaloids, and prevent cells from undergoing mitosis by disrupting microtubule polymerization, thus preventing cancerous growth. Microtubules are long, ropelike proteins that extend through the cell and move cellular components around. Microtubules are long polymers made of smaller units (monomers) of the protein tubulin. Microtubules are created during normal cell functions by assembling (polymerizing) tubulin components, and are disassembled when they are no longer needed. One of the important functions of microtubules is to move and separate chromosomes and other components of the cell for cell division (mitosis). Mitotic inhibitors interfere with the assembly and disassembly of tubulin into microtubule polymers. This interrupts cell division, usually during the mitosis (M) phase of the cell cycle when two sets of fully formed chromosomes are supposed to separate into daughter cells.

Vinca alkaloids

Are a set of anti-mitotic and anti-microtubule alkaloid agents originally derived from the periwinkle plant Catharanthus roseus (basionym Vinca rosea), and many species of vinca plants. They block beta-tubulin polymerization in a dividing cell.

Taxanes

Are complex terpenes produced by the plants of the genus Taxus (yews). Originally derived from the Pacific yew tree, they are now synthesized artificially. Their principal mechanism is the disruption of the cell's microtubule function by stabilizing microtubule formation. Microtubules are essential to mitotic reproduction, so through the inactivation of the microtubule function of a cell, taxanes inhibit the cell's division.

III.- Hormonal cytostatic antineoplastic agents

Sex hormone antagonists

These hormones are divided in three categories: antiandrogens, antiestrogens and antiprogestogens.

Antiandrogens

Estrogen-based Estramustine phosphate. EMP acts by a dual mechanism of action: 1) direct cytostatic activity via a number of actions; and 2) as a form of high-dose estrogen therapy via estrogen receptor-mediated antigonadotropic and functional antiandrogenic effects, this produce a suppression of gonadal androgen production and hence circulating levels of androgens such as testosterone; greatly increased levels of sex hormone-binding globulin and hence a decreased fraction of free androgens in the circulation; and direct antiandrogenic actions in prostate cells. Ex: Flutamida, Ciproterona.

Antiestrogens

Also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inhibiting or suppressing estrogen production. Example: Megestrol acetato.

Another category are the Selective estrogen receptor modulators: Are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists and antagonists (that is, full agonists and silent antagonists) is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues. Ex: Tamoxifen: It has mixed estrogenic and antiestrogenic activity, with its profile of effects differing by tissue.

Antiprogestogens

Corticosteroid-based: Prednimustine, it is used in chemotherapy in the treatment of leukemias and lymphomas. It is the ester formed from two other drugs, prednisolone and chlorambucil.

Aromatase inhibitors

Are a class of drugs used in the treatment of breast cancer in postmenopausal women and gynecomastia in men. Aromatase inhibitors work by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue. The main source of estrogen is the ovaries in premenopausal women, while in post-menopausal women most of the body's estrogen is produced in peripheral tissues (outside the CNS), and also a few CNS sites in various regions within the brain. Estrogen is produced and acts locally in these tissues, but any circulating estrogen, which exerts systemic estrogenic effects in men and women, is the result of estrogen escaping local metabolism and spreading to the circulatory system.

Aromatase is the enzyme that catalyzes a key aromatization step in the synthesis of estrogen. It converts the enone ring of androgen precursors such as testosterone, to a phenol, completing the synthesis of estrogen. As hormone postive breast and ovarian cancers require estrogen to grow, AIs are taken to either block the production of estrogen or block the action of estrogen on receptors. Ex: Aminoglutemida.

There are two types of aromatase inhibitors approved to treat breast cancer:

Irreversible steroidal inhibitors

Forms a permanent and deactivating bond with the aromatase enzyme. Example: exemestane.

Nonsteroidal inhibitors

inhibit the synthesis of estrogen via reversible competition. Examples: Triazoles anastrozoleand letrozole,

Gonadotropin-releasing hormone (GnRH) analogues

In 1972 Roger Guillemin and Andrew V. Schally discovered Gonadotropin-releasing hormone(GnRH)… this allowed the development of new drugs, among them: GnRH modulators, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor, this allowed the development of new drugs.

Examples:

Goserelin: Is a medication which is used to suppress production of the sex hormones (testosterone and estrogen). Leuprorelin: is a gonadotropin-releasing hormone (GnRH) analogue acting as an agonist at pituitary GnRH receptors. Agonism of GnRH receptors initially results in the stimulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion by the anterior pituitary ultimately leading to increased serum estradiol and testosterone levels via the normal physiology of the hypothalamic–pituitary–gonadal axis (HPG axis); however, because propagation of the HPG axis is incumbent upon pulsatile hypothalamic GnRH secretion, pituitary GnRH receptors become desensitised after several weeks of continuous leuprorelin therapy. This protracted downregulation of GnRH receptor activity is the targeted objective of leuprorelin therapy and ultimately results in decreased LH and FSH secretion, leading to hypogonadism and thus a dramatic reduction in estradiol and testosterone levels regardless of sex. In the treatment of prostate cancer, the initial increase in testosterone levels associated with the initiation of leuprorelin therapy is counterproductive to treatment goals. This effect is avoided with concurrent utilisation of 5α-reductase inhibitors, such as finasteride, which function to block the downstream effects of testosterone.

Glucocorticoids

Glucocorticoids are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell. The name "glucocorticoid" is a portmanteau (glucose + cortex + steroid) and is composed from its role in regulation of glucose metabolism, synthesis in the adrenal cortex, and its steroidal structure (see structure to the right). A less common synonym is glucocorticosteroid. Example: Prednisona.

Cancer immunotherapy

Cancer immunotherapy (sometimes called immuno-oncology) is the artificial stimulation of the immune system to treat cancer, improving on the immune system's natural ability to fight cancer. It is an application of the fundamental research of cancer immunology and a growing subspeciality of oncology. It exploits the fact that cancer cells often have tumor antigens, molecules on their surface that can be detected by the antibody proteins of the immune system, binding to them. The tumor antigens are often proteins or other macromolecules (e.g. carbohydrates). Normal antibodies bind to external pathogens, but the modified immunotherapy antibodies bind to the tumor antigens marking and identifying the cancer cells for the immune system to inhibit or kill. In 2018 James Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation.

Cytokines

Are a broad and loose category of small proteins (~5–20 kDa) that are important in cell signaling. Cytokines are peptides, and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine signaling, paracrine signaling and endocrine signaling as immunomodulating agents. Their definite distinction from hormones is still part of ongoing research. Cytokines used in antineoplastic treatments include the following:

Interleukins

Include Lymphokines.

Monoclonal antibodies (mAb or moAb)

Are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity, in that they bind to the same epitope (the part of an antigen that is recognized by the antibody). Given almost any substance, it is possible to produce monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. Monoclonal antibodies that bind only to cancer cell-specific antigens and induce an immune response against the target cancer cell.

MAbs approved by the FDA (for cancer) as of 2005 include the following:

• Alemtuzumab
• Bevacizumab
• Cetuximab
• Gemtuzumab ozogamicin
• Ipilimumab
• Ofatumumab
• Panitumumab
• Pembrolizumab
• Ranibizumab
• Rituximab
• Trastuzumab

IV- Cancer vaccines

Cancer vaccine is a vaccine, that either treats existing cancer or prevents development of a cancer.

a.- Vaccines that treat existing cancer are known as therapeutic cancer vaccines.

Bacillus Calmette–Guérin (BCG) vaccine: Was developed by Albert Calmette and Camille Guérin. The BCG vaccine was first used in humans in 1921. BCG has been one of the most successful immunotherapies. BCG vaccine has been the "standard of care for patients with bladder cancer (NMIBC)" since 1977.

b.- Vaccines that prevents development of a cancer.

Infections are the cause of 17.8% of human cancers, with 11.9% caused by one of seven viruses. These cancers might be easily prevented through vaccination (e.g., papillomavirus vaccines): Human papilloma virus (HPV) vaccines are vaccines that prevent infection by certain types of human papillomavirus: Available vaccines protect against either two, four or nine types of HPV. All vaccines protect against at least HPV types 16 and 18, which cause the greatest risk of cervical cancer. It is estimated that the vaccines may prevent 70% of cervical cancer, 80% of anal cancer, 60% of vaginal cancer, 40% of vulvar cancer and possibly some mouth cancer. They additionally prevent some genital warts, with the vaccines against HPV types 4 and 9 providing greater protection.

Glossary

Antigens (Ag): Are molecules that can induce the production nantibodies (Ab) or are specifically bound by a cell surface version of Ab ~ B cell antigen receptor (BCR), can also refer to any molecule or a linear molecular fragment after processing the native antigen that can be recognized by T-cell receptor (TCR). BCR and TCR are both highly variable antigen receptors diversified by somatic V(D)J recombination. Both T cells and B cells are cellular components of adaptive immunity.

Cancer: Is the uncontrolled growth of cells coupled with malignant behaviour: invasion and metastasis (among other features). It is caused by the interaction between genetic susceptibility and environmental factors. These factors lead to accumulations of genetic mutations in oncogenes (genes that control the growth rate of cells) and tumor suppressor genes (genes that help to prevent cancer), which gives cancer cells their malignant characteristics, such as uncontrolled growth.

Chemotherapeutic drugs In a broad sense are drugs that impair mitosis (cell division), effectively targeting fast-dividing cells. As these drugs cause damage to cells, they are termed cytotoxic. They prevent mitosis by various mechanisms including damaging DNA and inhibition of the cellular machinery involved in cell division.

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.

Also see

• Structural_Biochemistry

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