DirectHit
Encyclopedia
DirectHit is a pharmacodiagnostic test used to determine the tumor
sensitivity or resistance to drug
regimen
s recommended for the treatment of breast cancer
by the National Comprehensive Cancer Network
. It is a noninvasive test performed on small amounts of tissue
removed during the original surgery
lumpectomy
, mastectomy
, or core biopsy
. DirectHit was developed by CCC Diagnostics Inc., a biotechnology
company established by former researchers from Johns Hopkins University
. DirectHit was launched on 14 January 2010. Currently, it is the only available test for predicting treatment outcomes for anticancer chemotherapy
drugs for breast cancer.
technology. According to recent studies, quantitative immunofluorescence (QIF) can be applied to the standardization of protein
analysis, resulting in increased sensitivity and reproducibility. It is important to be able to quantitate the expression of predictive factors in breast cancer, because response to therapy is often dependent upon the concentration of particular proteins within the tissue.
DirectHit utilizes monoclonal antibodies
(mAb) corresponding to each biomarker to stain the tumor tissue samples. Slides are evaluated with a computerized, fluorescence
microscopy
system . Digital images are acquired through a CCCD camera. An algorithm was developed to process and analyze the digital images allowing direct relation between the amount of a specific protein within the cancer cell
s of the tumor and response to the corresponding drug. Quantitative measurement of up to five signals in a single cell
can be obtained.
Greenebaum Cancer Center
and Harborview Cancer Center in Baltimore
, MD. One key biomarker was selected as a correspondent to each drug, These biomarkers were identified as playing a significant role in cancer
processes and as bearing a mechanistic relation to the action of the specified drug. The drug groups used as treatment and their related biomarkers are as follows: Trastuzumab/HER-2/neu, Antiestrogens/Estrogen Receptor, Taxanes/beta-tubulin III, 5FU/Thymidylate Synthase.
In these trials DirectHit analysis of estrogen
receptor and HER-2/neu displayed a higher predictive accuracy for treatment outcomes with anti estrogen drugs and Trastuzumab than standard methods. In addition DirectHit displayed exceptional predictive accuracy for chemotherapy response (88%). DirectHit also displayed an extreme specificity for predictions of drug resistance (100%).
If a 50% treatment failure rate is assumed for standard chemotherapy, then the use of the DirectHit Test Panel for Breast Cancer could result in potential savings of approximately $466M in drug costs alone for 40,000 late stage cancer patients in the United States. If ancillary costs are also considered, DirectHit testing could result in a total savings of $566M - $666M.
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
sensitivity or resistance to drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
regimen
Regimen
A regimen is a plan, a regulated course such as a diet, exercise or medical treatment, designed to give a positive result. A low-salt diet is a regimen. A course of penicillin is a regimen.- History :...
s recommended for the treatment of 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...
by the National Comprehensive Cancer Network
National Comprehensive Cancer Network
National Comprehensive Cancer Network is an alliance of twenty-one cancer centers in the United States, most of which are designated by the National Cancer Institute as comprehensive cancer centers...
. It is a noninvasive test performed on small amounts of tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
removed during the original surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
lumpectomy
Lumpectomy
Lumpectomy is a common surgical procedure designed to remove a discrete lump, usually a benign tumor or breast cancer, from an affected man or woman's breast...
, mastectomy
Mastectomy
Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. Mastectomy is usually done to treat breast cancer; in some cases, women and some men believed to be at high risk of breast cancer have the operation prophylactically, that is, to prevent cancer...
, or core biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
. DirectHit was developed by CCC Diagnostics Inc., a biotechnology
Biotechnology
Biotechnology is a field of applied biology that involves the use of living organisms and bioprocesses in engineering, technology, medicine and other fields requiring bioproducts. Biotechnology also utilizes these products for manufacturing purpose...
company established by former researchers from Johns Hopkins University
Johns Hopkins University
The Johns Hopkins University, commonly referred to as Johns Hopkins, JHU, or simply Hopkins, is a private research university based in Baltimore, Maryland, United States...
. DirectHit was launched on 14 January 2010. Currently, it is the only available test for predicting treatment outcomes for anticancer chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
drugs for breast cancer.
Technology
DirectHit is based on quantitative immunofluorescenceImmunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
technology. According to recent studies, quantitative immunofluorescence (QIF) can be applied to the standardization of 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...
analysis, resulting in increased sensitivity and reproducibility. It is important to be able to quantitate the expression of predictive factors in breast cancer, because response to therapy is often dependent upon the concentration of particular proteins within the tissue.
DirectHit utilizes monoclonal antibodies
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
(mAb) corresponding to each biomarker to stain the tumor tissue samples. Slides are evaluated with a computerized, fluorescence
Fluorescence
Fluorescence is the emission of light by a substance that has absorbed light or other electromagnetic radiation of a different wavelength. It is a form of luminescence. In most cases, emitted light has a longer wavelength, and therefore lower energy, than the absorbed radiation...
microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
system . Digital images are acquired through a CCCD camera. An algorithm was developed to process and analyze the digital images allowing direct relation between the amount of a specific protein within the cancer cell
Cancer cell
Cancer cells are cells that grow and divide at an unregulated, quickened pace. Although cancer cells can be quite common in a person they are only malignant when the other cells fail to recognize and/or destroy them. In the past a common belief was that cancer cells failed to be recognized and...
s of the tumor and response to the corresponding drug. Quantitative measurement of up to five signals in a single cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
can be obtained.
Clinical Trials
The DirectHit Panel for Breast Cancer was validated in retrospective clinical trials conducted at The University of MarylandUniversity of Maryland
When the term "University of Maryland" is used without any qualification, it generally refers to the University of Maryland, College Park.University of Maryland may refer to the following:...
Greenebaum Cancer Center
University of Maryland Greenebaum Cancer Center
The University of Maryland Marlene and Stewart Greenebaum Cancer Center is a National Cancer Institute-designated cancer center located in Baltimore, Maryland.- Quick Facts :* 2,500 Admissions* 45,000 Outpatient visits* 125 Clinical trials...
and Harborview Cancer Center in Baltimore
Baltimore
Baltimore is the largest independent city in the United States and the largest city and cultural center of the US state of Maryland. The city is located in central Maryland along the tidal portion of the Patapsco River, an arm of the Chesapeake Bay. Baltimore is sometimes referred to as Baltimore...
, MD. One key biomarker was selected as a correspondent to each drug, These biomarkers were identified as playing a significant role in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
processes and as bearing a mechanistic relation to the action of the specified drug. The drug groups used as treatment and their related biomarkers are as follows: Trastuzumab/HER-2/neu, Antiestrogens/Estrogen Receptor, Taxanes/beta-tubulin III, 5FU/Thymidylate Synthase.
In these trials DirectHit analysis of estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
receptor and HER-2/neu displayed a higher predictive accuracy for treatment outcomes with anti estrogen drugs and Trastuzumab than standard methods. In addition DirectHit displayed exceptional predictive accuracy for chemotherapy response (88%). DirectHit also displayed an extreme specificity for predictions of drug resistance (100%).
Cost
The cost of the DirectHit Panel for Breast Cancer is $3500. The use of DirectHit could result in significant cost savings because physicians will be able to customize treatment regimens for patients, eliminating ineffective drugs that would have otherwise been prescribedIf a 50% treatment failure rate is assumed for standard chemotherapy, then the use of the DirectHit Test Panel for Breast Cancer could result in potential savings of approximately $466M in drug costs alone for 40,000 late stage cancer patients in the United States. If ancillary costs are also considered, DirectHit testing could result in a total savings of $566M - $666M.
See also
- Johns Hopkins UniversityJohns Hopkins UniversityThe Johns Hopkins University, commonly referred to as Johns Hopkins, JHU, or simply Hopkins, is a private research university based in Baltimore, Maryland, United States...
- the university that developed this method of breast cancer testing - National Comprehensive Cancer NetworkNational Comprehensive Cancer NetworkNational Comprehensive Cancer Network is an alliance of twenty-one cancer centers in the United States, most of which are designated by the National Cancer Institute as comprehensive cancer centers...
- a US government initiative for cancer research
Further reading
- Giltrane GM, Molinaro, A, Cheng, H, Robinson A, Turbin D, Gelmon K, Huntsman D, and Rimm DL. Comparison of Qantitative Immunofluorescence with Conventional Methods for Her-2/neu testing With Respect to Trastuzumab Therapy in Metastatic Breast Cancer. Archives of Pathology and Laboratory Medicine, 2008; 132, 1635-1647.
- Bertucci F, Birnbaum D, and Goncalves A. Proteomics of Breast Cancer, Principles and Potential Clinical Applications. Molecular & Cellular Proteomics, 2006; 5, 1772-1786.