This page represents findings from a research project based on data from 23 different biopharmaceutical companies.
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Protein therapy is a medical treatment showing much promise that is still in mostly investigatory stages. The idea is similar to gene therapy, but unlike gene therapy, protein therapy delivers protein to the body in specific amounts, as would be ordinarily present, to help repair illnesses, treat pain or remake structures. It is important to view much of what is known about protein therapy today as still highly investigational, but scientists do regard it with hope, since some early studies have suggested it may be of benefit in may instances.
Proteins are not that difficult to make. They might be created in a variety of ways, via labs, growth in animals or culturing in different types of cells. Since many illnesses show insufficient protein levels in one or more body systems, simply adding whole and strong proteins back is not much of a logical leap. There are some issues with this, though, including the fact that delivery of the protein has to be carefully assessed.
On this last front, it’s not always possible to deliver a protein unless it goes directly to the source it needs to aid. Sending it through the blood or the digestive tract could degrade it, and it might never reach its intended target. The matter of delivery remains complicated, and in many tests attempt is made for direct delivery to the intended area, such as the heart or brain.
When on site, the hope is that the protein, which is not present in sufficient levels, will act exactly as it is designed to do. For instance, some studies have evaluated use of certain proteins in addressing cardiovascular disease. Especially when veins or arteries become blocked, the right types of proteins might address this issue by going to work on building new passages for bloodflow. Some doctors feel that protein therapy of this type might eventually be so successful that it could eliminate the need for complicated surgeries like bypass surgery.
There have been some human trials with protein therapy, but many trials are still conducted on animals. Early trials in humans have shown promise in some areas. Physicians and other medical researchers look to these studies with considerable hope, though it still could be years before any one protein therapy treatment was approved for use by regulating agencies, or became widely used.
Some of the potential benefits of this therapy include curing chronic pain conditions, arresting illnesses that causes degradation of tissues, restoring or rebuilding tissue, and intervening early at fetal stages to prevent expression of certain birth defects. These same issues may be addressed with gene therapy too, though many scientists contend protein therapy is presently more advanced and easier to use. Both therapies have a likely role in the future of medicine.
Cancer immunotherapy (immuno-oncology) is the use of the immune system to treat cancer. Immunotherapies fall into three main groups: cellular, antibody and cytokine. They exploit the fact that cancer cells often have subtly different molecules on their surface that can be detected by the immune system. These molecules, known as cancer antigens, are most commonly proteins, but also include molecules such as carbohydrates. Immunotherapy is used to provoke the immune system into attacking the tumor cells by using these antigens as targets.
Antibody therapies are the most successful immunotherapy, treating a wide range of cancers. Antibodies are proteins produced by the immune system that bind to a target antigen on the cell surface. In normal physiology the immune system uses them to fight pathogens. Each antibody is specific to one or a few proteins. Those that bind to cancer antigens are used to treat cancer. Cell surface receptors are common targets for antibody therapies and include the CD20, CD274, and CD279. Once bound to a cancer antigen, antibodies can induce antibody-dependent cell-mediated cytotoxicity, activate the complement system, or prevent a receptor from interacting with its ligand, all of which can lead to cell death. Multiple antibodies are approved to treat cancer, including Alemtuzumab, Ipilimumab, Nivolumab, Ofatumumab, and Rituximab.
Cellular therapies, also known as cancer vaccines, usually involve the removal of immune cells from the blood or from a tumor. Immune cells specific for the tumor are activated, cultured and returned to the patient where the immune cells attack the cancer. Cell types that can be used in this way are natural killer cells, lymphokine-activated killer cells, cytotoxic T cells and dendritic cells. The only cell-based therapy approved in the US is Dendreon's Provenge, for the treatment of prostate cancer.
Interleukin-2 and interferon-α are examples of cytokines, proteins that regulate and coordinate the behaviour of the immune system. They have the ability to enhance anti-tumor activity and thus can be used as cancer treatments. Interferon-α is used in the treatment of hairy-cell leukaemia, AIDS-related Kaposi's sarcoma, follicular lymphoma, chronic myeloid leukaemia and malignant melanoma. Interleukin-2 is used in the treatment of malignant melanoma and renal cell carcinoma.
Proteins enter the nucleus through the nuclear pore complex. Once in the nucleus, some proteins, such as transcriptional regulators, can turn genes on or off, and change the composition of the cell and its function to meet the demands of its environment. This process of protein import into the nucleus is highly controlled and regulated by the expression or function of single cargoes, transport receptors, or the transport channels themselves. Thus, these components of the import process have an impact on transport capacity, which subsequently affects gene expression, signal transduction, and cell growth and development. With such a key position in the process of cell growth, it is reasonable to hypothesize that alterations in nuclear protein transport may play an important role in pathological cell conditions that have abnormal cell growth as a central feature. Indeed, there are now sufficient data to demonstrate that alterations in nuclear protein transport participate in alterations in cell proliferation and hypertrophy. Further study is needed to provide definitive proof that changes in nuclear protein import directly participate in the pathogenesis of diseases such as hypertension, atherosclerosis, cancer, viral infection, and diabetes. However, the data to date have, on select occasions, led to a clear association of alterations in nuclear transport with disease states. Furthermore,this research has led to the important identification of new targets within the process of nuclear protein import that hold therapeutic promise to inhibit viral replication, to improve drug delivery during cancer therapy, and, in general, to modify cell growth and viability during disease conditions.
Drugs directed at plasma membrane receptors target environment-cell interactions and are the mainstay of clinical pharmacology. Decoding mechanisms that govern intracellular signaling has recently opened new therapeutic avenues for interventions at cytosol-organellar interfaces. The nuclear envelope and nuclear transport machinery have emerged central in the discovery and development of experimental therapeutics capable of modulating cellular genetic programs. Insight into nucleocytoplasmic exchange has unmasked promising anticancer, antiviral, and anti-inflammatory strategies.
Gene therapy is the therapeutic delivery of nucleic acid polymers into a patient's cells as a drug to treat disease. Gene therapy could be a way to fix a genetic problem at its source. The polymers are either expressed as proteins, interfere with protein expression, or possibly correct genetic mutations.
The most common form uses DNA that encodes a functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a "vector", which carries the molecule inside cells.
Gene therapy was conceptualized in 1972, by authors who urged caution before commencing human gene therapy studies. The first gene therapy experiment approved by the US Food and Drug Administration (FDA) occurred in 1990, when Ashanti DeSilva was treated for ADA-SCID. By January 2014, some 2,000 clinical trials had been conducted or approved.
Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers' attention, although as of 2014, it was still largely an experimental technique. These include treatment of retinal disease Leber's congenital amaurosis, X-linked SCID, ADA-SCID, adrenoleukodystrophy, chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), multiple myeloma, haemophilia and Parkinson's disease. Between 2013 and April 2014, US companies invested over $600 million in the field.
The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of certain cancers. In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia. In 2012 Glybera, a treatment for a rare inherited disorder, became the first treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells) that is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen and many antigens are recognized by the same TCR.
The TCR is composed of two different protein chains (that is, it is a heterodimer). In man 95% of T cells the TCR consists of an alpha (α) and beta (β) chain, whereas in 5% of T cells the TCR consists of gamma and delta (γ/δ) chains. This ratio changes during ontogeny and in diseased states as well as in different species.
When the TCR engages with antigenic peptide and MHC (peptide/MHC), the T lymphocyte is activated through signal transduction, that is, a series of biochemical events mediated by associated enzymes, co-receptors, specialized adaptor molecules, and activated or released transcription factors.
T cell-based adoptive immunotherapy has been shown to be a promising treatment for various types of cancer. However, adoptive T cell therapy currently requires the custom isolation and characterization of tumor-specific T cells from each patient-a process that can be not only difficult and time-consuming but also often fails to yield high-avidity T cells, which together have limited the broad application of this approach as a clinical treatment. Employing T cell receptor (TCR) gene therapy as a component of adoptive T cell therapy strategies can overcome many of these obstacles, allowing autologous T cells with a defined specificity to be generated in a much shorter time period. Initial studies using this approach have been hampered by a number of technical difficulties resulting in low TCR expression and acquisition of potentially problematic specificities due to mispairing of introduced TCR chains with endogenous TCR chains. The last several years have seen substantial progress in our understanding of the multiple facets of TCR gene therapy that will have to be properly orchestrated for this strategy to succeed.
Cellular metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. Cellular metabolism involves complex sequences of controlled biochemical reactions, better known as metabolic pathways. These processes allow organisms to grow and reproduce, maintain their structures, and respond to environmental changes.
The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed into another by a sequence of enzymes. Enzymes are crucial to metabolism and allow the fine regulation of metabolic pathways to maintain a constant set of conditions in response to changes in the cell's environment, a process known as homeostasis.
The metabolic properties of cancer cells diverge significantly from those of normal cells. Energy production in cancer cells is abnormally dependent on aerobic glycolysis. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics such as increased fatty acid synthesis and increased rates of glutamine metabolism. Emerging evidence shows that many features characteristic to cancer cells, such as dysregulated Warburg-like glucose metabolism, fatty acid synthesis and glutaminolysis are linked to therapeutic resistance in cancer treatment. Therefore, targeting cellular metabolism may improve the response to cancer therapeutics and the combination of chemotherapeutic drugs with cellular metabolism inhibitors may represent a promising strategy to overcome drug resistance in cancer therapy. Recently, several review articles have summarized the anticancer targets in the metabolic pathways and metabolic inhibitor-induced cell death pathways, however, the dysregulated metabolism in therapeutic resistance, which is a highly clinical relevant area in cancer metabolism research, has not been specifically addressed. From this unique angle, this review article will discuss the relationship between dysregulated cellular metabolism and cancer drug resistance and how targeting of metabolic enzymes, such as glucose transporters, hexokinase, pyruvate kinase M2, lactate dehydrogenase A, pyruvate dehydrogenase kinase, fatty acid synthase and glutaminase can enhance the efficacy of common therapeutic agents or overcome resistance to chemotherapy or radiotherapy.
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.
Most of the antiviral drugs now available are designed to help deal with HIV, herpes viruses, the hepatitis B and C viruses, and influenza A and B viruses. Researchers are working to extend the range of antivirals to other families of pathogens.
Designing safe and effective antiviral drugs is difficult, because viruses use the host's cells to replicate. This makes it difficult to find targets for the drug that would interfere with the virus without also harming the host organism's cells. Moreover, the major difficulty in developing vaccines and anti-viral drugs is due to viral variation.
The emergence of antivirals is the product of a greatly expanded knowledge of the genetic and molecular function of organisms, allowing biomedical researchers to understand the structure and function of viruses, major advances in the techniques for finding new drugs, and the intense pressure placed on the medical profession to deal with the human immunodeficiency virus (HIV), the cause of the deadly acquired immunodeficiency syndrome (AIDS) pandemic.
The first experimental antivirals were developed in the 1960s, mostly to deal with herpes viruses, and were found using traditional trial-and-error drug discovery methods. Researchers grew cultures of cells and infected them with the target virus. They then introduced into the cultures chemicals which they thought might inhibit viral activity, and observed whether the level of virus in the cultures rose or fell. Chemicals that seemed to have an effect were selected for closer study.
This was a very time-consuming, hit-or-miss procedure, and in the absence of a good knowledge of how the target virus worked, it was not efficient in discovering effective antivirals which had few side effects. Only in the 1980s, when the full genetic sequences of viruses began to be unraveled, did researchers begin to learn how viruses worked in detail, and exactly what chemicals were needed to thwart their reproductive cycle.
A central nervous system (CNS) disease can affect either the brain or the spinal cord, resulting in neurological or psychiatric disorders. Causes of CNS diseases are trauma, infections, degeneration, autoimmune disorders, structural defects, tumors, and stroke. Here we focus on neurodegenerative diseases, mood disorders, schizophrenia, and autism. See details here.
Neurodegenerative diseases are featured by progressive dysfunction and death of cells in selected areas in the nervous system. These include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, and Amyotrophic lateral sclerosis (ALS). Alzheimer's disease causes memory loss, personality changes, dementia and, ultimately, death. Parkinson's disease causes tremor, stiffness, and impaired control of movement resulting from loss of dopamine. Huntington's is a hereditary disease caused by a dominant mutation on either of the two copies of Huntingtin gene. The mutation results in neuronal degeneration in the frontal lobe of the brain. The most characteristic symptom of Huntington's disease is jerky, random, and uncontrollable movements called chorea. Amyotrophic lateral sclerosis is a motor neurons degenerative disease with no known cause. QIAGEN's Alzheimer's disease PCR arrays can be used to detect AD-related gene expressions.
Extra- and intra-cellular accumulation of misfolded proteins, such as beta-amyloid, tau, alpha-synuclein, TDP-43, are the hallmarks of many neurodegenerative disorders. The abnormal protein dynamics associated with defective degradation are due to deficiency of the ubiquitin-proteosomal-autophagy system. Alzheimer's disease is regarded as a protein disease, caused by accumulation of abnormally folded beta-amyloid protein and tau proteins in the brain. Mitochondrial dysfunction is another prominent feature of various neurodegenerative diseases because the most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. In general, disruption of neuronal Golgi apparatus and transport, deregulation of molecular chaperones, defective protein degradation, oxidative stress and free radical formation, impaired bioenergetics and mitochondrial dysfunction, deregulation of neurotransmitters, neurotrophins, and neuroinflammatory processes (such as Multiple Sclerosis, please see the review under Cytokines & Inflammation) can all lead to programmed cell death. It is worth noting that methylation of CpG islands is one of the important mechanisms that promote the accumulation of oxidized DNA. For example, environmental influences during brain development can inhibit DNA methyltransferases, thus hypomethylating promoters of genes associated with Alzheimer's disease, causing the accumulation of beta-amyloid precursor protein. QIAGEN provides a broad range of PCR arrays to study Apoptosis, Mitochondria, Mitochondrial Energy Metabolism, Ubiquitination Pathway, Unfolded Protein Response, Antioxidative Stress and Antioxidant Defense, Neurotransmitter Receptors and Regulators, Neurotrophins and Receptors, and Neuroscience Ion Channels and Transporters.
Conventional gene therapy has focused largely on gene replacement in target cells. However, progress from basic research to the clinic has been slow for reasons relating principally to the challenges of heterologous DNA delivery and regulation in vivo. Alternative approaches targeting RNA have the potential to circumvent some of these difficulties, particularly as the active therapeutic molecules are usually short oligonucleotides and the target gene transcript is under endogenous regulation. RNA-based strategies offer a series of novel therapeutic applications, including altered processing of the target pre-mRNA transcript, reprogramming of genetic defects through mRNA repair, and the targeted silencing of allele- or isoform-specific gene transcripts.
RNA targeting is emerging as a powerful alternative to conventional gene replacement therapies for the treatment of genetic disorders. Although an emerging field, RNA modification has the potential to circumvent some of the shortcomings of standard gene therapy methods, including: (i) low efficiency of gene transfer; (ii) limitations on transgene size, specifically an inability to deliver genomic size loci; (iii) insertional mutagenesis and integration-associated events; and (iv) immune responses and toxicity due to vectors. Moreover, some disease situations could be more amenable to correction by RNA targeting, such as autosomal dominant diseases, where introduction of a functional gene does not address expression of the dominant mutant transcript. Similarly, in disorders of RNA processing, such as aberrant splicing, it may be preferable to repair the endogenous splicing pattern, which could also correct multiple alternative isoforms. More importantly, RNA targeting has unique potential for therapeutic modification of native mRNA transcripts within a normal regulatory environment. The potential of such approaches ranges from elimination of the mRNA in question to modification of the mature mRNA product by the removal or addition of natural elements or exons and to repair of the mRNA transcript by the addition of foreign mRNA elements to create a chimeric gene product. Many of the effector molecules underpinning these novel methods have their origins in natural biochemical pathways that have been discovered in recent years.
Dramatic advances in understanding of the roles RNA plays in normal health and disease have greatly expanded over the past 10 years and have made it clear that scientists are only beginning to comprehend the biology of RNAs. It is likely that RNA will become an increasingly important target for therapeutic intervention; therefore, it is important to develop strategies for therapeutically modulating RNA function. Antisense oligonucleotides are perhaps the most direct therapeutic strategy to approach RNA. Antisense oligonucleotides are designed to bind to the target RNA by well-characterized Watson-Crick base pairing, and once bound to the target RNA, modulate its function through a variety of postbinding events. This review focuses on the molecular mechanisms by which antisense oligonucleotides can be designed to modulate RNA function in mammalian cells and how synthetic oligonucleotides behave in the body.
Allergen immunotherapy, also known as desensitization or hypo-sensitization, is a medical treatment for some types of allergies. It is useful for environmental allergies, allergies to insect bites, and asthma. Its benefit for food allergies is unclear and thus not recommended. Immunotherapy involves exposing people to larger and larger amounts of allergen in an affect to change the immune system's response.
Meta-analyses have found that injections of allergens under the skin is effective in the treatment in allergic rhinitis in children and in asthma. The benefits may last for years after treatment is stopped. It is generally safe and effective for allergic rhinitis, allergic conjunctivitis, allergic forms of asthma, and stinging insects. The evidence also supports the use of sublingual immunotherapy for rhinitis and asthma but it is less strong. In this form the allergen is given under the tongue and people often prefer it to injections. Immunotherapy is not recommended as a stand alone treatment for asthma.
Side effects during treatment are usually local and mild and can usually be eliminated by adjusting the dosage. Anaphylaxis has occurred on rare occasions and this is why treatment should only be administered in a medical environment.
Discovered by Leonard Noon and John Freeman in 1911, allergen immunotherapy is the only medicine known to tackle not only the symptoms but also the causes of respiratory allergies. A detailed diagnosis is necessary to identify the allergens involved. It is currently being studied as a possible treatment for eczema and food allergies in children.
Enzyme replacement therapy (ERT) is a medical treatment replacing an enzyme in patients in whom that particular enzyme is deficient or absent. Usually this is done by giving the patient an intravenous (IV) infusion containing the enzyme. Enzyme replacement therapy is currently available for some lysosomal diseases: Gaucher disease, Fabry disease, MPS I, MPS II (Hunter syndrome), MPS VI and Glycogen storage disease type II. Enzyme replacement therapy does not correct the underlying genetic defect, but increases the concentration of enzyme in which the patient is deficient. In Pompe disease the ERT replaces the deficient lysosomal enzyme acid alpha-glucosidase (GAA) Digestive enzymes can be replaced orally.
The concept of enzyme replacement therapy for lysosomal storage diseases was enunciated by de Duve in 1964. However, much cell biology had to be learned before lysosomal enzymes could be developed into pharmaceuticals. A model system, consisting of cultured skin fibroblasts from patients with mucopolysaccharidoses (MPS), showed that their defective glycosaminoglycan catabolism could be corrected by factors derived from cells of a different genotype. The corrective factors were identified as lysosomal enzymes with a special feature, or recognition signal, that would permit efficient uptake. As the recognition signal was absent from a number of lysosomal enzymes secreted by fibroblasts from patients with I-cell disease (a monogenic disorder), it was postulated to be a post-translational modification of the lysosomal enzymes. It was subsequently shown to be a carbohydrate and identified as mannose-6-phosphate (M6P), which was recognized by ubiquitous M6P receptors. A second model system was the clearance, in vivo, of lysosomal enzymes from plasma. The recognition signal for this system was identified as mannose, and clearance was shown to be mediated by the mannose receptor of the reticuloendothelial system. This second system was immediately put to use for the treatment of Gaucher disease type I, in which macrophages are the affected cells. Native, and later recombinant, glucocerebrosidase was modified to expose terminal mannose residues; it became the first successful pharmaceutical for a lysosomal storage disease. Recombinant lysosomal enzymes containing the M6P signal have been developed (or are in the advanced stages of development) into pharmaceuticals for the treatment of Fabry disease, MPS I, MPS II, MPS VI and Pompe disease.
Endocrine therapy, also known as hormone therapy, is a treatment that adds, blocks, or removes hormones. For certain conditions (such as diabetes or menopause), hormones are given to adjust low hormone levels. To slow or stop the growth of certain cancers (such as prostate and breast cancer), synthetic hormones or other drugs may be given to block the body’s natural hormones. Sometimes surgery is needed to remove the gland that makes a certain hormone. Also called hormonal therapy, hormone therapy, and hormone treatment.
Hormonal therapy in oncology is hormone therapy for cancer and is one of the major modalities of medical oncology (pharmacotherapy for cancer), others being cytotoxic chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine system through exogenous administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones (hormone antagonists). Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.
Hormonal therapy is used for several types of cancers derived from hormonally responsive tissues, including the breast, prostate, endometrium, and adrenal cortex. Hormonal therapy may also be used in the treatment of paraneoplastic syndromes or to ameliorate certain cancer- and chemotherapy-associated symptoms, such as anorexia. Perhaps the most familiar example of hormonal therapy in oncology is the use of the selective estrogen-response modulator tamoxifen for the treatment of breast cancer, although another class of hormonal agents, aromatase inhibitors, now have an expanding role in that disease.
In molecular biology and pharmacology, a small molecule is a low molecular weight organic compound that may help regulate a biological process, with a size on the order of 10−9 m. Most drugs are small molecules.
The upper molecular weight limit for a small molecule is approximately 900 daltons, which allows for the possibility to rapidly diffuse across cell membranes so that they can reach intracellular sites of action. In addition, this molecular weight cutoff is a necessary but insufficient condition for oral bioavailability. Finally, a lower molecular weight cutoff of 500 daltons (as part of the "rule of five") has been recommended for small molecule drug development candidates based on the observation that clinical attrition rates are significantly reduced if the molecular weight is kept below this 500 dalton limit.
Small molecules may also be used as research tools to probe biological function as well as leads in the development of new therapeutic agents. Some can inhibit a specific function of a multifunctional protein or disrupt protein–protein interactions.
The discovery and development of small molecule cancer drugs has been revolutionised over the last decade. Most notably, we have moved from a one-size-fits-all approach that emphasized cytotoxic chemotherapy to a personalised medicine strategy that focuses on the discovery and development of molecularly targeted drugs that exploit the particular genetic addictions, dependencies and vulnerabilities of cancer cells. These exploitable characteristics are increasingly being revealed by our expanding understanding of the abnormal biology and genetics of cancer cells, accelerated by cancer genome sequencing and other high-throughput genome-wide campaigns, including functional screens using RNA interference.
Epigenetics refers to the study of long-term changes in gene expression, which may or may not be heritable, which are not caused by changes to the DNA sequence. These changes can result from chemical modifications to DNA and chromatin, or can be caused by changes to several regulatory mechanisms. Epigenetic markings can be inherited in some cases, and can change in response to environmental stimuli over the course of an organism's life.
Many diseases are known to have a genetic component, but the epigenetic mechanisms underlying many conditions are still being discovered. A significant number of diseases are known to change the expression of genes within the body, and epigenetic involvement is a plausible hypothesis for how they do this. These changes can be the cause of symptoms to the disease. Several diseases, especially cancer, have been suspected of selectively turning genes on or off, thereby resulting in a capability for the tumorous tissues to escape the host’s immune reaction.
In applying cancer gene discoveries to treatment, investigators are focusing on the pathways through which altered cancer genes work because the genes themselves can often be elusive to therapy. Many of the gene mutations driving cancers are in tumor suppressor genes. The loss of these genes removes important brakes on cell growth, but it’s difficult to attack a target that’s already missing.
Sometimes, however, tumor suppressor genes become ineffective without being mutated. The causes of this are known as epigenetic alterations. Biochemical changes to the environment of the DNA, rather than directly to it, can silence key genes. Investigators have found that using drugs to block this biochemical activity provides an opportunity to reverse the changes and reset the DNA to its pre-cancer environment.
Monoclonal antibodies (mAb or moAb) are monospecific antibodies that are made by identical immune cells that are all clones of a unique parent cell, in contrast to polyclonal antibodies which are made from several different immune cells. Monoclonal antibodies have monovalent affinity, in that they bind to the same epitope.
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. This has become an important tool in biochemistry, molecular biology and medicine. When used as medications, the non-proprietary drug name ends in -mab (see "Nomenclature of monoclonal antibodies"), and many immunotherapy specialists use the word mab anacronymically.
A monoclonal antibody is a laboratory-produced molecule that's carefully engineered to attach to specific defects in cancer cells. Monoclonal antibodies mimic the antibodies the body naturally produces as part of its immune system's response to germs, vaccines and other invaders.