Differentiation therapy

Differentiation therapy
Specialty	oncology

Differentiation therapy is an approach to treating advanced cancers in which malignant cells are encouraged to differentiate into more mature forms using pharmacological agents. The basis of the therapy stems from the tendency of malignant tumor cells to assume a less specialized, stem cell-like dedifferentiated state.[1]

Leukemia

The approach was motivated by noticing that leukemia cells fail to differentiate and fully mature.[2]

By 2001 encouraging clinical results were seen.[3]

The first differentiation agent found to be successful was all-trans-retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL).[1]

Other cancers

The process of cancer spreading (metastasis) involves tumour cells undergoing an epithelial-to-mesenchymal transition (EMT) to invade and spread, followed by a mesenchymal-to-epithelial transition (MET) at remote sites.

Other agents investigated (pre-clinically) to encourage MET include cholera toxin (CTx) and forskolin (Fsk).[4]

References

Sell, Stewart. (2004). "Stem cell origin of cancer and differentiation therapy". Critical Reviews in Oncology/Hematology. 51 (1): 1–28. doi:10.1016/j.critrevonc.2004.04.007. PMID 15207251.
Nowak, D.; Stewart, D.; Koeffler, H. P. (2009). "Differentiation therapy of leukemia: 3 decades of development". Blood. 113 (16): 3655–65. doi:10.1182/blood-2009-01-198911. PMC 2943835. PMID 19221035.
Leszczyniecka, M; Roberts, T; Dent, P; Grant, S; Fisher, P. B. (2001). "Differentiation therapy of human cancer: Basic science and clinical applications". Pharmacology & Therapeutics. 90 (2–3): 105–56. doi:10.1016/s0163-7258(01)00132-2. PMID 11578655.
Pattabiraman, D. R.; Bierie, B.; Kober, K. I.; Thiru, P.; Krall, J. A.; Zill, C.; Reinhardt, F.; Tam, W. L.; Weinberg, R. A. (2016). "Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability". Science. 351 (6277): aad3680. doi:10.1126/science.aad3680. PMC 5131720. PMID 26941323.

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[Sell2004-1] Sell, Stewart. (2004). "Stem cell origin of cancer and differentiation therapy". Critical Reviews in Oncology/Hematology. 51 (1): 1–28. doi:10.1016/j.critrevonc.2004.04.007. PMID 15207251.

[Nowak2009-2] Nowak, D.; Stewart, D.; Koeffler, H. P. (2009). "Differentiation therapy of leukemia: 3 decades of development". Blood. 113 (16): 3655–65. doi:10.1182/blood-2009-01-198911. PMC 2943835. PMID 19221035.

[3] Leszczyniecka, M; Roberts, T; Dent, P; Grant, S; Fisher, P. B. (2001). "Differentiation therapy of human cancer: Basic science and clinical applications". Pharmacology & Therapeutics. 90 (2–3): 105–56. doi:10.1016/s0163-7258(01)00132-2. PMID 11578655.

[Patt2016-4] Pattabiraman, D. R.; Bierie, B.; Kober, K. I.; Thiru, P.; Krall, J. A.; Zill, C.; Reinhardt, F.; Tam, W. L.; Weinberg, R. A. (2016). "Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability". Science. 351 (6277): aad3680. doi:10.1126/science.aad3680. PMC 5131720. PMID 26941323.