Novel therapy in Acute myeloid leukemia (AML): moving toward targeted approaches

Abstract

Acute myeloid leukemia (AML) is a heterogenous and complex disease characterized by rapid cellular proliferation, an aggressive clinical course, and generally high mortality. While progress has been made in the understanding of the genetic and molecular biology of the disease, the standard of care for patients had only changed minimally over the past 40 years. Recently, rapid movement of potentially useful agents from bench to bedside has translated into new therapies either recently approved or in clinical trials. These therapies include improved chemotherapies, mutationally targeted inhibitors, pro-apoptotic agents, microenvironment targeting molecules, cell cycle checkpoint inhibitors, and epigenetic regulators. Furthermore, advances in immunotherapy employ monoclonal and bispecific antibodies, chimeric antigen receptor (CAR) T cells, checkpoint inhibitors, and vaccines provide an alternative pathway for AML treatment. In this review, we discuss the recent results of completed or ongoing clinical trials with these novel therapeutic agents in AML.

CDK6 Inhibition: A Novel Approach in AML Management

“…CDK6 binds to chromatin and drives their transcription in a kinase-dependent manner [27]. Although AKT and AURORA kinase inhibitors have significant therapeutic potential in AML, single-agent activity has not been proven overly effective; respective dual inhibitors (FLT3/AURK or FLT3/AKT) are in preclinical development [99,100]. Inhibitors of AURK and AKT signaling, however, effectively synergized with palbociclib in FLT3-ITD and -D835Y-expressing cells.…”

Nanocarriers as Magic Bullets in the Treatment of Leukemia

“…Giving ruxolitinib and CPX-351 in combination may work better in treating patients with secondary acute myeloid leukemia compared to CPX-351 alone. Another drug currently under evaluation in combination with CPX-351 is Palbociclib, a CDK4/6 inhibitor already approved for the treatment of breast cancer [166]. Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.…”

CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

“…Inhibitors for BCL-2, venetoclax, and Bruton tyrosine kinase, ibrutinib and acalabrutinib, are playing major roles in therapy for chronic lymphoid leukemia as well as in mantle cell lymphoma [27][28][29][30]. Recently, FLT3 inhibitors and inhibitors of isocitrate dehydrogenases (IDH1 and IDH2) significantly enhanced the armamentarium for AML therapy [31][32][33][34][35]. TKIs targeting a variety of oncoproteins, such as EGFR, ALK, HER2, FGFR, VEGFR, RET, MET, to name a few, have brought revolutions in the therapy of non-small cell lung cancer, breast cancer, bladder cancer, liver cancer, and renal cell carcinoma [5,6,[36][37][38][39][40][41][42].…”