Section 5 Targeted Therapies

*Acute Leukemias*

haematol.2016.151910

doi:10.2217/ijh.13.4

10.1002/cpt.1962

2017;102(3):529-540. doi:10.3324/

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[42] Khanal, Nabin & Banskota, Shristi & Bhatt, Vijaya. (2020). Novel treatment paradigms in acute myeloid leukemia. Clinical Pharmacology & Therapeutics. 10.1002/cpt.1962**.** doi:

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**Chapter 14**

**Abstract**

**1. Introduction**

recently entered the clinical practice.

*1.1.1 FLT3 tyrosine kinase inhibitors*

Leukemia

*Vasko Graklanov*

Target Therapy in Acute Myeloid

Acute myeloid leukemia (AML) is the most common form of acute leukemia in elderly patients. Over the past four decades the basic therapeutic armamentarium was the standard cytotoxic treatment. The new insights in understanding the pathogenesis of AML was the momentum that revolutionized the treatment landscape in AML. The last five years unprecedented growth has been seen in the number of target therapy drugs for the treatment of AML. These new drugs did not just have a clinical benefit as single agents but also have improved AML patient outcomes if combined with conventional cytotoxic therapy. Here, we review recent advances in target-based therapy for patients with AML focusing on their mechanism of action

**Keywords:** acute myeloid leukemia, target therapy, FLT3 inhibitors, IDH inhibitors, pro-apoptotic agents, smoothened inhibitors, checkpoint inhibitors, CD33-targeted

Acute myeloid leukemia (AML) is a heterogeneous malignant disease, characterized by uncontrolled proliferation with impaired differentiation of myeloid progenitor cells and aggressive clinical course. In the past two decades the treatment landscape of AML underwent significant changes due to explosive growth in knowledge of the molecular pathways involved in the AML origin and course evolution. This increased new data and understanding of the pathogenesis of AML, facilitated the development of new drugs in the treatment of AML, particularly the creation of drugs that target the disease on a molecular level. Encouraging efficacy of targeted therapy when combined with the traditional chemotherapy have resulted in big improvement to AML treatment and survival. In this chapter, we will discuss the drugs used in treatment of AML, including targeted treatment strategies that have

Full-length human FLT3 was cloned from a pre-B cell library in 1993 [1], from a CD34+ hematopoietic stem cell-enriched library [2], and is located on chromosome 13q12 [3]. FLT3 is a member of class III receptor tyrosine kinases (RTK) [4] and its activation leads to promotion of cell survival, proliferation, and differentiation

and the results from already published clinical trials.

therapy, E-selectin inhibitors, Polo-like kinase inhibitors

**1.1 Signaling and kinase pathway mutations inhibitors**
