As personalized medicine develops, high complexity laboratory diagnostic testing has more and more importance to identify these specific molecular targets for each individual case.
Plainview, NY (PRWEB) January 25, 2013
January 2013 – Leukemias and lymphomas are hematological malignancies, originating from the blood cell forming organs, such as the bone marrow and the lymph nodes. More than 100,000 cases of leukemia and lymphoma are diagnosed in the United States every year resulting in more than 50,000 deaths. Survival rates for cancer have improved dramatically over the past decades, and the five-year survival rate (the percentage of people who survive five years from the date of diagnosis) for all age groups is 56.5% for leukemia; 86.3% for Hodgkin lymphoma; and 69.5% for non-Hodgkin lymphoma. In the past twenty years the improvement in diagnostic methods for early diagnosis, as well as new therapeutic options, have contributed to better survival rates.
“A major disadvantage of conventional cancer treatments, such as chemotherapy and radiation, is that they do not discriminate between tumor cells and dividing normal cells. Therefore these therapies may have serious side effects,” explains Dr. Zsuzsanna Vegh-Goyarts, assistant director of the Hematology-Oncology Flow Cytometry department at Acupath Laboratories, a leader in high complexity testing and molecular genetics. In the past several decades researchers have been trying to find more cancer specific treatments, agents that specifically bind to and destroy the cancer cells and have minimal toxicity to the normal cells. “As personalized medicine develops, high complexity laboratory diagnostic testing has more and more importance to identify these specific molecular targets for each individual case,” she adds.
Monoclonal antibodies (MoAbs) were first used in animal models for targeting tumor cells. They are protein molecules that bind to targets on the cell surface with great specificity. The first MoAb based clinical trials started almost thirty years ago, and today many MoAb based drugs are available for the treatment of cancer and other diseases. MoAbs are conjugated with toxins, drugs or radioisotopes allowing them to deliver the killing agents specifically to the cancer cells. They are effective and less toxic than conventional therapies.
“The presence of the target molecule has to be screened for on the patients’ cancer cells before MoAb treatment can be applied. Testing with advanced laboratory methods such as flow cytometry identifies the target on the cancer cells in each case to ensure that the appropriate drug is used,” says Dr. Vegh-Goyarts. Rituximab (Rituxan) was one of the first MoAbs that was approved for B cell non-Hodgkin lymphomas in 1997. It binds to the CD20 molecules on B cells and induces the killing of the lymphoma cells. Some other MoAb based drugs are targeting the CD33 molecule (e.g. Mylotag) and used for the treatment of acute myeloid leukemia (AML). Anti-CD52 molecule (e.g. Campath) may be used for the treatment of chronic lymphoid leukemia (CLL) and for some T cell lymphomas, and anti -CD30 (e.g. Adcetris) can be used for Hodgkin lymphomas. The expression of these CD molecules on the neoplastic cells has to be tested by flow cytometry or immunohistochemistry before therapeutic decisions can be made.
In recent years another approach for targeted therapy was the introduction of tyrosine kinase inhibitors. Tyrosine kinases are enzymes that are part of the signaling pathways of cells, and their function is to keep cellular proliferation in control. When these molecules become activated due to mutations, tumor cells start to proliferate, persist and spread. Targeted inhibition of these enzymes with small synthetic molecules, or with MoAbs, can halt the division of the neoplastic cells and stop tumor growth and metastasis. “As an example, the BCR/ABL fusion gene, that is the result of a chromosomal translocation, produces a mutated tyrosine kinase that transforms normal cells to leukemic cells, resulting in chronic myeloid leukemia (CML) or in some cases in acute lymphoid leukemia (ALL). If this mutation is identified by molecular testing, the mutated kinase can be specifically targeted with a highly selective synthetic kinase inhibitor such as Gleevec (Imatinib). Another example of a targeted kinase molecule is FLT-3 in acute leukemia (AML). These molecular targets are identified in the molecular diagnostic laboratory using PCR before the specific treatment can be initiated,” explains Dr. Vegh-Goyarts.
HER-2 neu is another example of targeted tyrosine kinases. When this gene is overexpressed, it activates cell proliferation, which occurs in about 30% of breast cancers. “Herceptin is a MoAb that binds to the HER-2 molecule and stops the division of the cancer cells. Breast cancer biopsies are tested by immunohistochemistry or by FISH for Her-2 neu, and if tested positive, the patient may be eligible for Herceptin treatment,” says Dr Vegh-Goyarts.
In the last twenty years many genes that regulate cancer progression have been identified that can serve as therapeutic targets. Antisense oligonucleotides (ASO) are new types of molecules that bind to cancer specific targets. ASOs are single stranded DNA-like molecules that are designed to be complementary to a selected mRNA. “ASO molecules block the translation of a gene to a protein. The most promising targets for ASO therapy are molecules that are overexpressed during cancer progression,” explains Dr Vegh-Goyarts. One of these targets is the BCL-2 oncogene which, if rearranged, enhances cancer cell survival by inhibiting the natural cycle of cell death in various cancer types. The BCL-2 specific ASO, G3139, is complementary to the BCL-2 mRNA, thus blocking the synthesis of the BCL-2 protein. The first clinical trial of G3139 started in 1997 for non-Hodgkin’s lymphomas and later it was tested for CLL, multiple myeloma and some solid tumors. Other ASO targeted therapies are also in the development phase or in clinical trials. “The rearranged BCL-2 gene has to be tested by molecular diagnostic methods, such as FISH or PCR before the patient can be eligible for this type of treatment,” she adds.
As there are new cancer specific drugs in the pipeline, there will be more and more demand for high complexity diagnostic laboratory testing, not just to diagnose disease, but to screen for these specific therapeutic targets. These specific technologies, flow cytometry and molecular methods such as FISH and PCR, are currently available at Acupath Laboratories Inc.
Zsuzsanna Vegh-Goyarts Ph.D. is the assistant director of the Hematology-Oncology Flow Cytometry department at Acupath Laboratories, Inc., a leader in high complexity testing and molecular genetics.
Acupath Laboratories, Inc. is a Plainview, New York, specialty medical laboratory engaged in cutting-edge diagnostics. http://www.acupath.com