The observation that one round of chemotherapy does not kill all the cells in a tumor is a well-known yet poorly understood phenomenon called “fractional cell kill. ” The fractional kill hypothesis states that a defined chemotherapy concentration  applied for a defined time period  will kill a constant fraction of the cells in a population, independent of the absolute number of cells Berenbaum, M. C. (1972). "In vivo determination of the fractional kill of human tumor cells by chemotherapeutic agents." Cancer Chemother Rep 56(5): 563-71.Skipper, H. E. (1979). "Historic milestones in cancer biology: a few that are important in cancer treatment (revisited)." Semin Oncol 6(4): 506-14.Chabner, B. and D. L. Longo (2006). Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia, Lippincott Willians & Wilkins.. In solid tumors, poor access of the tumor to the drug can limit the fraction of tumor cells killed, but the validity of the fractional kill hypothesis has also been established in animal models of leukemia  as well as in human leukemia and lymphoma, where drug access is less of an issue. Because only a fraction of the cells die with each treatment, repeated doses must be administered to continue to reduce the size of the tumor . Current chemotherapy regimens apply drug treatment in cycles, with the frequency and duration of treatments limited by toxicity to the patient . The goal is to reduce the tumor population to zero with successive fractional kills . For example, assuming a 99\% kill per cycle of chemotherapy, a tumor of 1011 cells would be reduced to less than one cell with six treatment cycles: 1011 * 0.016 < 1 . However, the tumor can also re-grow during the intervals between treatments, limiting the net reduction of each fractional kill Skeel, R. T. (2003). Handbook of Cancer Chemotherapy, Lippincott Williams & Wilkins.. A recent paper by Spencer et al.Spencer, S. L., S. Gaudet, et al. (2009). "Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis." Nature. URL raises the possibility that cell-to-cell variability in protein concentrations may contribute to fractional killing in the case of treatment with TRAIL (TNF-related apoptosis inducing ligand). TRAIL is a ligand native to the human body that is currently being developed as a cancer treatment. Spencer et al. observed fractional killing at a single cell level in several cell lines, even in genetically identical populations grown in homogenous environments. This paper ruled out the conventional explanation (cell cycle effects) in two of these cell lines, and provided evidence supporting the hypothesis that random variation in cellular initial conditions causes some cells to die while allowing others to survive. Reference 
In oncology, the fact that one round of chemotherapy does not kill all the cells in a tumor is a poorly understood phenomenon called fractional kill, or fractional cell kill. The fractional kill hypothesis states that a defined chemotherapy concentration , applied for a defined time period , will kill a constant fraction of the cells in a population, independent of the absolute number of cells Berenbaum, M. C. (1972). "In vivo determination of the fractional kill of human tumor cells by chemotherapeutic agents." Cancer Chemother Rep 56(5): 563-71.Skipper, H. E. (1979). "Historic milestones in cancer biology: a few that are important in cancer treatment (revisited)." Semin Oncol 6(4): 506-14.Chabner, B. and D. L. Longo (2006). Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia, Lippincott Willians & Wilkins.. In solid tumors, poor access of the tumor to the drug can limit the fraction of tumor cells killed, but the validity of the fractional kill hypothesis has also been established in animal models of leukemia , as well as in human leukemia and lymphoma, where drug access is less of an issue. Because only a fraction of the cells die with each treatment, repeated doses must be administered to continue to reduce the size of the tumor . Current chemotherapy regimens apply drug treatment in cycles, with the frequency and duration of treatments limited by toxicity to the patient . The goal is to reduce the tumor population to zero with successive fractional kills . For example, assuming a 99\% kill per cycle of chemotherapy, a tumor of 1011 cells would be reduced to less than one cell with six treatment cycles: 1011 * 0.016 < 1 . However, the tumor can also re-grow during the intervals between treatments, limiting the net reduction of each fractional kill Skeel, R. T. (2003). Handbook of Cancer Chemotherapy, Lippincott Williams & Wilkins.. A recent paper by Spencer et al.Spencer, S. L., S. Gaudet, et al. (2009). "Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis." Nature. URL raises the possibility that cell-to-cell variability in protein concentrations may contribute to fractional killing in the case of treatment with TRAIL (TNF-related apoptosis inducing ligand). TRAIL is a ligand native to the human body that is currently being developed as a cancer treatment. Spencer et al. observed fractional killing at a single cell level in several cell lines, even in genetically identical populations grown in homogeneous environments. This paper ruled out the conventional explanation (cell cycle effects) in two of these cell lines, and provided evidence supporting the hypothesis that random variation in cellular initial conditions causes some cells to die while allowing others to survive. References Category:Oncology Category:Cell biolog
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Category:Oncology Category:Cell biolog