Targeting phosphatidylinositol 3-kinase signaling in acute myelogenous leukemia

Camilla Evangelisti, Cecilia Evangelisti, Daniela Bressanin, Francesca Buontempo, Francesca Chiarini, Annalisa Lonetti, Marina Soncin, Antonino Spartà, James A. McCubrey, Alberto M. Martelli

Research output: Contribution to journalArticle

Abstract

Introduction: Despite continuous advances in our knowledge of the biology of acute myelogenous leukemia (AML), the prognosis of AML patients treated with standard chemotherapy is still poor, especially in the elderly. Therefore, there is a need for novel targeted and less toxic therapies, particularly for patients who develop resistance to traditional chemotherapeutic drugs. Constitutively active phosphatidylinositol 3-kinase (PI3K) signaling characterizes many types of tumors, including AML, where it negatively influences response to therapeutic treatments. Areas covered: The literature data showed that small inhibitor molecules targeting PI3K signaling induced cell cycle arrest, apoptosis and decreased drug-resistance in AML cells. PI3K inhibitors were also capable of targeting leukemic initiating cells (LICs), the most relevant target for leukemia eradication, whereas they tended to spare healthy hematopoietic stem cells. Expert opinion: Data emerging from pre-clinical settings suggest that the PI3K pathway is critically involved in regulating proliferation, survival and drug-resistance of AML cells. Therefore, we propose that novel drugs targeting this signaling pathway may offer a novel and less toxic treatment option for AML patients, most likely in combination with a lower dosage of traditional chemotherapeutic agents or other innovative therapeutic agents.

Original languageEnglish
Pages (from-to)921-936
Number of pages16
JournalExpert Opinion on Therapeutic Targets
Volume17
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Acute myelogenous leukemia
  • Drug-resistance
  • Leukemia initiating cells
  • PI3K signaling

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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  • Cite this

    Evangelisti, C., Evangelisti, C., Bressanin, D., Buontempo, F., Chiarini, F., Lonetti, A., Soncin, M., Spartà, A., McCubrey, J. A., & Martelli, A. M. (2013). Targeting phosphatidylinositol 3-kinase signaling in acute myelogenous leukemia. Expert Opinion on Therapeutic Targets, 17(8), 921-936. https://doi.org/10.1517/14728222.2013.808333