MiCK Assay™

Chemotherapy of a malignant tumor aims to either completely eliminate the tumor cells or substantially reduce their number. Chemotherapeutic agents’ ability to kill tumor cells makes this goal achievable. The tumor cells of an individual patient, however, may be sensitive to one chemotherapeutic agent but not to another. Oncologists currently use an empirical approach to the selection of treatment protocols – the selection of a therapeutic agent is based on statistical data obtained in large clinical studies.

 

For instance, a clinical study shows that agent A helps 60 leukemia patients out of 100 to keep their disease in check, or, as it is usually said, to achieve complete remission. With agent B, complete remission is seen in 35 patients while with agent C complete remission is achieved in 5 patients. Thus, oncologists selecting between agent A, agent B, and agent C, would rather use agent A because agent A is expected to be effective in 60% of leukemia patients. What about the remaining 40% of patients who are statistically not expected to respond to agent A, but would better benefit from agent B or agent C? For them, the use of agent A will result in treatment failure. In other words, their tumor cells will not be killed effectively enough, complete remission will not be achieved and the disease will progress. It may be reasonable for patients in this group to utilize agent B or agent C after agent A fails. Unfortunately, it is not always possible to use another treatment protocol with the same patient. First, all chemotherapeutic agents are highly toxic substances and patients may not survive another round of treatment. Besides, time is lost and the disease may progress beyond its treatable phase. To complicate the picture, it is unclear whether the patient’s tumor cells would be more sensitive to agent B or agent C.

The American Cancer Society estimates that approximately 1.22 million new cancer cases are diagnosed every year. For more than 700,000 of these patients, some form of chemotherapy will be used in the treatment plan.

The treatment outcome for cancer patients could be dramatically improved if oncologists would include agents that are effective against tumor cells of a specific patient in the first line of therapy.

The Microculture Kinetics (MiCK) assay for apoptosis helps oncologist discriminate between effective and ineffective chemotherapeutic agents prior to their use in a patient’s treatment. MiCK assay helps oncologists to create an individual treatment protocol that includes a drug or drug combination that is most effective in killing tumor cells of an individual patient.

How does MiCK assay work? Over the last 10 years it has been shown in multiple studies that chemotherapeutic agents exert their antitumor activity by triggering apoptosis, a distinct mode of cell death that is accompanied by dramatic changes in the appearance of tumor cells.

The figure above is a photomicrograph of a “healthy” tumor cell (at left) and three other tumor cells at various stages of apoptotic death cased by exposure to a chemotherapeutic agent. The photo demonstrates that cells dying by apoptosis form big blebs on the outer surface of the cell. Formation of these blebs results in a change in the cells’ light scattering properties. A sophisticated device called a spectrophotometer can detect the resulting change in the optical properties of apoptotic cells.

Tumor cells undergoing apoptosis manifest an increased side light scattering as compared to “healthy” tumor cells. The MiCK assay of apoptosis is based on frequent measurements of the optical density of tumor cells exposed to multiple chemotherapeutic agents. If a chemotherapeutic agent kills tumor cells by apoptosis, the spectrophotometer will “see” and report accumulation of apoptotic tumor cells as a steep increase in the optical density. On the computer screen, this steep increase in the optical density appears as a so called “apoptotic curve”. Data generated by the spectrophotometer are fed to the computer and automatically analyzed in order to determine the extent of the tumor cells’ apoptosis. This allows for the identification of a chemotherapeutic agent which causes the most extensive apoptosis in tumor cells. If a patient has no medical contraindications, this agent may be included in the patient’s treatment protocol.

In no way can MiCK assay’s results substitute for the medical judgment of an oncologist. The MiCK assay is a powerful tool arming oncologists with valuable information on the drug sensitivity profile of a specific cancer patient. However, the final decision on whether a specific agent should or should not be included in the patient’s treatment protocol, is always made by the patient’s physician.