Targeted therapy

Targeted Therapy

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Targeted therapy

Targeted therapy is a type of medication

Medication

A pharmaceutical drug, also referred to as medicine or medicament, can be loosely defined as any substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease....
that blocks the growth of cancer cell

Cancer Cell

Cancer Cell is the first Cell Press journal to focus on a specific disease field, with an editorial scope spanning from basic to clinical-oriented researches and a strong emphasis on translational research....
s by interfering with specific targeted molecules needed for carcinogenesis

Carcinogenesis

'Carcinogenesis' , is the process by which normal cell are transformed into cancer cells.Cell division is a physiological process that occurs in almost all tissues and under many circumstances....
and tumor

Tumor

A tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells . Tumor is not synonymous with cancer. A tumor can be Benign neoplasm, Carcinoma in situ or malignant, whereas cancer is by definition malignant....
growth, rather than by simply interfering with rapidly dividing cells (eg. with traditional chemotherapy

Chemotherapy

Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer....
). Targeted cancer therapies may be more effective than current treatments and less harmful to normal cells.

Some have challenged use of the term, stating that drugs usually associated with the term are insufficiently selective.

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Encyclopedia

Targeted therapy is a type of medication

Medication

Cancer Cell

Carcinogenesis

Tumor

Chemotherapy

Types

The main categories of targeted therapy are small molecule
Small molecule

In pharmacology, a small molecule is a small organic compound that is biologically active but is not a polymer. This term is very loosely used and it may or may not include monomers or metabolites, in fact it is generally used to denote molecules that are not protein which play a endogenous or exogenous biological role, such as cell signalli...
s and monoclonal antibodies.

Small molecules

Imatinib mesylate
Imatinib

Imatinib is a medication used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate ....
(Gleevec, also known as STI–571) is approved for chronic myelogenous leukemia
Chronic myelogenous leukemia

Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood....
, gastrointestinal stromal tumor
Gastrointestinal stromal tumor

A gastrointestinal stromal tumor is a rare disease tumor of the gastrointestinal tract . They are a type of mesenchyme tumor and typically defined as tumors whose behavior is driven by genetic mutations in the CD117 gene or PDGFRA gene, and may or may not staining positively for Kit....
and some other types of cancer. Early clinical trials indicate that imatinib may be effective in treatment of dermatofibrosarcoma protuberans
Dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans is a rare neoplasm of the dermis layer of the skin, and is classified as a sarcoma. In many respects, the disease behaves as a benign tumor, but in 2-5% of cases it can metastasis, so it should be considered to have malignant potential....
.
Gefitinib
Gefitinib

Gefitinib is a medication used in the treatment of certain types of cancer. Acting in a similar manner to erlotinib , gefitinib selectively targets the mutant proteins in malignant cells....
(Iressa, also known as ZD1839), targets the epidermal growth factor receptor
Epidermal growth factor receptor

The epidermal growth factor receptor is the Cell membrane receptor for members of the epidermal growth factor family of extracellular protein ligand ....
(EGFR) tyrosine kinase
Tyrosine kinase

A tyrosine kinase is an enzyme that can transfer a phosphate group from Adenosine triphosphate to a tyrosine residue in a protein. Tyrosine kinases are a subgroup of the larger class of protein kinases....
and is approved in the U.S. for non small cell lung cancer
Lung cancer

Lung cancer is a disease of uncontrolled cell growth in tissue of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs....
. EGFR is also overexpressed in the cells of other solid tumors, such as lung and breast cancers. This leads to inappropriate activation of the apoptotic
Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed Cell death involves a series of biochemical events leading to a characteristic cell Morphology and death, in more specific terms, a series of biochemical events that lead to a variety of morphological changes, including Bleb , changes...
Ras
Ras

In the field of molecular biology, Ras is the name of a protein, the gene that encodes it, and the family and superfamily of proteins to which it belongs....
signal transduction
Signal transduction

In biology, 'signal transduction' refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemistry chemical reaction inside the cell, which are carried out by enzymes, activated by Second messenger systems, resulting in a signal tran...
cascade, eventually leading to uncontrolled cell proliferation.Gefitinib inhibits EGFR tyrosine kinase by binding to the adenosine triphosphate
Adenosine triphosphate

This article is about the chemical used by cells as an energy carrier. For other uses, see ATP .Adenosine-5'-triphosphate is a multifunctional nucleotide, and plays an important role in cell biology as a coenzyme that is the "molecule unit of currency" of intracellular energy transfer....
(ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited.
Erlotinib
Erlotinib

Erlotinib hydrochloride is a medication used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is marketed in the United States by Genentech and OSI Pharmaceuticals and elsewhere by Roche under the tradename Tarceva....
(marketed as Tarceva). Erlotinib inhibits epidermal growth factor receptor
Epidermal growth factor receptor

The epidermal growth factor receptor is the Cell membrane receptor for members of the epidermal growth factor family of extracellular protein ligand ....
, and works through a similar mechanism as gefitinib. Erlotinib has been shown to increase survival in metastatic non small cell lung cancer
Lung cancer

Lung cancer is a disease of uncontrolled cell growth in tissue of the lung. This growth may lead to metastasis, which is the invasion of adjacent tissue and infiltration beyond the lungs....
when used as second line therapy. Because of this finding, erlotinib has replaced gefitinib in this setting.
Bortezomib
Bortezomib

Bortezomib is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma....
(Velcade) is an apoptosis
Apoptosis

Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Programmed Cell death involves a series of biochemical events leading to a characteristic cell Morphology and death, in more specific terms, a series of biochemical events that lead to a variety of morphological changes, including Bleb , changes...
-inducing drug that causes cancer cells to undergo cell death by interfering with proteins. It is approved in the U.S. to treat multiple myeloma
Multiple myeloma

Multiple myeloma is a cancer of plasma cells. These immune system cells are formed in bone marrow, are numerous in lymphatics and produce antibody....
that has not responded to other treatments.

Newer BCL-2
Bcl-2

Bcl-2 is the prototype for a family of mammalian genes and the proteins they produce. They govern mitochondrial outer membrane permeabilization and can be either pro-apoptosis or anti-apoptotic ....
antagonists, such as Obatoclax, ABT-263, and Gossypol
Gossypol

Gossypol C30H30O8 is a polyphenol derived from the cotton plant . Gossypol is a polyphenolic aldehyde that permeates cells and acts as an inhibitor for several dehydrogenase enzymes....
.

The selective estrogen receptor modulator
Selective estrogen receptor modulator

Selective Estrogen Receptor Modulators are a class of medication that acts on the estrogen estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonist and Receptor antagonist is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate est...
tamoxifen
Tamoxifen

Tamoxifen is an orally taken selective estrogen receptor modulator that is used in the treatment of breast cancer and is currently the world's largest selling drug for that purpose....
has been described as the foundation of targeted therapy.

Monoclonal antibodies

Several are in development and a few have been licenced by the FDA. Examples of licenced monoclonal antibodies include:

Rituximab
Rituximab

Rituximab, sold under the trade names Rituxan and MabThera, is a Chimera monoclonal antibody against the protein CD20. Rituximab is used in the treatment of B cell non-Hodgkin's lymphoma, B-cell leukemias, and some autoimmune disorders....
targets CD20 found on B cells. It is used in non Hodgkin lymphoma
Lymphoma

Lymphoma is a type of cancer that originates in lymphocytes of the immune system. They often originate in lymph nodes, presenting as an enlargement of the node ....
Trastuzumab
Trastuzumab

Trastuzumab is a monoclonal antibody that interferes with the HER2/neu Receptor .The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off....
(Herceptin) targets the Her2/neu
HER2/neu

HER2/neu stands for "Human Epidermal growth factor Receptor 2" and is a protein giving higher aggressiveness in breast cancers. It is a member of the ErbB protein family, more commonly known as the ErbB....
(also known as ErbB2) receptor expressed in some types of breast cancer
Breast cancer

Breast cancer is a cancer that starts in the Cell of the breast in women and men. Worldwide, breast cancer is the second most common type of cancer after lung cancer and the fifth most common cause of cancer death....
Cetuximab
Cetuximab

Cetuximab is a chimeric monoclonal antibody, an epidermal growth factor receptor enzyme inhibitor, given by intravenous therapy for treatment of metastatic colorectal cancer and head and neck cancer....
(marketed as Erbitux) targets the epidermal growth factor receptor. It is used in the treatment of colon cancer and non-small cell lung cancer.
Bevacizumab
Bevacizumab

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor-A . It is used in the treatment of cancer, where it inhibits tumor growth by blocking the formation of new blood vessels ....
(marketed as Avastin) targets circulating VEGF ligand. It is approved for use in the treatment of colon cancer, breast cancer
Breast cancer

Breast cancer is a cancer that starts in the Cell of the breast in women and men. Worldwide, breast cancer is the second most common type of cancer after lung cancer and the fifth most common cause of cancer death....
, non-small cell lung cancer and is investigational in the treatment of sarcoma
Sarcoma

A sarcoma is a cancer of the connective tissue resulting in mesoderm proliferation.This is in contrast to Carcinoma, which are of Epithelium origin ....
.

Progress and future

Many oncologists believe that targeted therapies are the chemotherapy of the future. As solid tumor cancer continues to be viewed as a chronic

Chronic (medicine)

In medicine, a chronic disease is a disease that is long-lasting or recurrent. The term chronic describes the Course of the disease, or its rate of onset and development....
condition, methods for long-term treatment, with less side-effects, continue to be investigated.

In the U.S., the National Cancer Institute

National Cancer Institute

The National Cancer Institute is part of the United States Federal government's National Institutes of Health. The NCI is a federally funded research and development center, one of eight agencies that compose the United States Public Health Service in the United States Department of Health and Human Services....
's (MTDP) to identify and evaluate molecular targets that may be candidates for drug development.

The next stage of targeted therapies will focus on finding which patients will respond to which targeted therapies. This is called the identification of "sub-populations". The route to identify these sub-populations is through biomarkers and surrogate endpoints.

One agent which seems to be promising is cannabidiol

Cannabidiol

Cannabidiol, also known as CBD, is a Cannabinoids found in Cannabis. It is a major constituent of the plant, representing up to 40% in its extracts....
, a non-toxic substance found in cannabis

Cannabis

Cannabis is a genus of flowering plants that includes three putative species, Cannabis sativa L., Cannabis indica Lam., and Cannabis ruderalis Janisch....
which has been found to reduce growth and invasiveness of cancer cells in vitro

In vitro

In vitro refers to the technique of performing a given procedure in a controlled environment outside of a living organism. Some may argue that in vitro refers to a process that is created in a "test tube"; however, Robert Kail and John Cavanaugh on page 58 in the 4th edition of Human Development: A Life-Span View cite that in fact th...
.

External links

Green, Mark New England Journal of Medicine (May 20, 2004)
Journal of Clinical Oncology (April 10, 2005)
Lynch, Thomas New England Journal of Medicine (May 20, 2004)