Stratified medicine
Encyclopedia
Stratified medicine is the management of a group of patients with shared biological characteristics by using molecular diagnostic testing to select the best therapy
in order to achieve the best possible medicinal outcome for that group.
” in the Wall Street Journal, which promised targeting drugs for each unique genetic profile
– but in fact, the first step towards a more individualized pharmacotherapy
was already taken several decades before this manifesto. With the discovery of the estrogen receptor
in the 1960s and the introduction of the anti-estrogen tamoxifen
in the 1970s the road was prepared for a more individualized treatment of patients within breast cancer
. The test for hormone receptor
status became an important stratification
factor for anti-estrogen treatment. In the 1990s another targeted drug was introduced which was aimed at a selected group of cancer patients: women whose breast cancer tumors overexpressed the human epidermal growth factor receptor 2 (HER2). The drug was the monoclonal antibody trastuzumab
(Herceptin, Genentech, CA, USA) which was specifically targeted toward the HER2 protein of the tumor cells. Also for trastuzumab a pharmacodiagnostic test
/ companion diagnostic test played an important role in relation to treatment stratification. This was the immunohistochemical assay for the HER2 protein
(HercepTest, Dako, Glostrup, Denmark).
The article by Robert Langreth and Michael Waldholz was the first to describe personalized medicine
in the way it is perceived today – a combination of an identifiable target in the individual and a drug directed towards this target. In spite of the general perception of the term being “personalized medicine”, it might so far be more correct to use the term “stratified medicine”, as suggested by several authors. Personalized medicine is the situation where the treatment is completely tailored to meet the requirements of the unique individual patient based on a “complete” molecular diagnostic profile, whereas stratified medicine use molecular testing to stratify the patients with shared biological characteristics to the best treatment, often using only a single or few molecular markers.
that should be reflected in the choice of pharmacotherapy, thus resulting in an improved treatment outcome. As we see it right now, the implementation of personalized medicine will be a stepwise process where stratification of patients into biological subgroups will be the first important step. Here drug and pharmacodiagnostic/ companion diagnostic testing are very closely linked together, and the test result is used to stratify the patient to the best treatment. Clear examples of stratified medicine are patients with breast cancer who can be grouped according to their biological characteristics, such as estrogen receptor positivity or HER2 overexpression, and be treated according to these characteristics with an anti estrogens or a HER2 inhibitor. The move from blockbuster medicine towards personalized medicine will be a stepwise process, where stratified medicine will be the first goal to be reached.
Therapy
This is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...
in order to achieve the best possible medicinal outcome for that group.
Personalized medicine is the goal
In 1999 Robert Langreth and Michael Waldholz announced the “New Era of Personalized MedicinePersonalized medicine
Personalized medicine is a medical model emphasizing in general the customization of healthcare, with all decisions and practices being tailored to individual patients in whatever ways possible...
” in the Wall Street Journal, which promised targeting drugs for each unique genetic profile
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
– but in fact, the first step towards a more individualized pharmacotherapy
Pharmacotherapy
Pharmacotherapy is the treatment of disease through the administration of drugs. As such, it is considered part of the larger category of therapy....
was already taken several decades before this manifesto. With the discovery of the estrogen receptor
Estrogen receptor
Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...
in the 1960s and the introduction of the anti-estrogen tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
in the 1970s the road was prepared for a more individualized treatment of patients within breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. The test for hormone receptor
Hormone receptor
A hormone receptor is a receptor protein on the surface of a cell or in its interior that binds to a specific hormone. The hormone causes many changes to take place in the cell....
status became an important stratification
Genetic association
Genetic association is the occurrence, more often than can be readily explained by chance, of two or more traits in a population of individuals, of which at least one trait is known to be genetic....
factor for anti-estrogen treatment. In the 1990s another targeted drug was introduced which was aimed at a selected group of cancer patients: women whose breast cancer tumors overexpressed the human epidermal growth factor receptor 2 (HER2). The drug was the monoclonal antibody 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, Genentech, CA, USA) which was specifically targeted toward the HER2 protein of the tumor cells. Also for trastuzumab a pharmacodiagnostic test
Pharmacodiagnostic testing
Pharmacodiagnostic testing is pre-treatment testing performed in order to determine whether or not a patient is likely to respond to a given therapy. This type of test is classified as a predictive test and is a wikt:prerequisite for the implementation of stratified and personalized medicine....
/ companion diagnostic test played an important role in relation to treatment stratification. This was the immunohistochemical assay for the HER2 protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
(HercepTest, Dako, Glostrup, Denmark).
The article by Robert Langreth and Michael Waldholz was the first to describe personalized medicine
Personalized medicine
Personalized medicine is a medical model emphasizing in general the customization of healthcare, with all decisions and practices being tailored to individual patients in whatever ways possible...
in the way it is perceived today – a combination of an identifiable target in the individual and a drug directed towards this target. In spite of the general perception of the term being “personalized medicine”, it might so far be more correct to use the term “stratified medicine”, as suggested by several authors. Personalized medicine is the situation where the treatment is completely tailored to meet the requirements of the unique individual patient based on a “complete” molecular diagnostic profile, whereas stratified medicine use molecular testing to stratify the patients with shared biological characteristics to the best treatment, often using only a single or few molecular markers.
Stratified medicine as the next step
The philosophy behind personalized medicine is that every patient has a unique biology and pathophysiologyPathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
that should be reflected in the choice of pharmacotherapy, thus resulting in an improved treatment outcome. As we see it right now, the implementation of personalized medicine will be a stepwise process where stratification of patients into biological subgroups will be the first important step. Here drug and pharmacodiagnostic/ companion diagnostic testing are very closely linked together, and the test result is used to stratify the patient to the best treatment. Clear examples of stratified medicine are patients with breast cancer who can be grouped according to their biological characteristics, such as estrogen receptor positivity or HER2 overexpression, and be treated according to these characteristics with an anti estrogens or a HER2 inhibitor. The move from blockbuster medicine towards personalized medicine will be a stepwise process, where stratified medicine will be the first goal to be reached.
Leaving the blockbuster era
We are slowly approaching the post blockbuster era, but it may take some time before we arrive there, and the promise about “targeting drugs for each unique genetic profile”, as announced by Robert Langreth and Michael Waldholz in Wall Street Journal in 1999, will be a scenario still awaiting further progress within molecular diagnostic testing and drug development. However, stratifications of patients with shared biological characteristics by using pharmacodiagnostic/companion diagnostic testing will be an important step forward in realization of a more safe and effective pharmacotherapy.External links
- WIN Symposium in Personalized Cancer Medicine A major annual event presenting breakthrough scientific technologies and achievements in personalized cancer medicine, with a special focus on individualized treatment and early diagnosis of cancer, 7-9 July 2010, Paris, France.
- Personalized Medicine Coalition