Kinase Inhibition in Relapsed/Refractory Leukemia and Lymphoma Settings: Recent Prospects into Clinical Investigations

Abstract

Cancer is still a major barrier to life expectancy increase worldwide, and hematologic neoplasms represent a relevant percentage of cancer incidence rates. Tumor dependence of continuous proliferative signals mediated through protein kinases overexpression instigated increased strategies of kinase inhibition in the oncologic practice over the last couple decades, and in this review, we focused our discussion on relevant clinical trials of the past five years that investigated kinase inhibitor (KI) usage in patients afflicted with relapsed/refractory (R/R) hematologic malignancies as well as in the pharmacological characteristics of available KIs and the dissertation about traditional chemotherapy treatment approaches and its hindrances. A trend towards investigations on KI usage for the treatment of chronic lymphoid leukemia and acute myeloid leukemia in R/R settings was observed, and it likely reflects the existence of already established treatment protocols for chronic myeloid leukemia and acute lymphoid leukemia patient cohorts. Overall, regimens of KI treatment are clinically manageable, and results are especially effective when allied with tumor genetic profiles, giving rise to encouraging future prospects of an era where chemotherapy-free treatment regimens are a reality for many oncologic patients.

Coronary atherosclerosis and chemotherapy: From bench to bedside

“…Anthracyclines, including Adriamycin (doxorubicin), Adriamycin liposomes, and daunorubicin, are widely used in the treatment of various malignant tumors, and clinical trials of these drugs began in the 1960s. The cardiotoxic effects of anthracyclines were first identified by Machado et al ( 13 ) in a clinical trial involving 94 patients (68 children and 26 adults) with various tumor types. This trial summarized the clinical experience with daunorubicin ( 13 ).…”

“…The cardiotoxic effects of anthracyclines were first identified by Machado et al ( 13 ) in a clinical trial involving 94 patients (68 children and 26 adults) with various tumor types. This trial summarized the clinical experience with daunorubicin ( 13 ). Ewer et al ( 14 ) reported the cardiovascular adverse effects of anthracyclines in a multicenter retrospective analysis of 4,018 patients.…”

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution

“…Regardless of being intrinsic or acquired, MDR pathways provide tumors with the ability to bypass the effects of proliferation and survival impairment imposed by cytotoxic treatments through mechanisms such as increased drug efflux caused by overexpression of the transmembrane transporters of the ATP binding cassette (ABC) family, upregulation of DDR proteins, epigenetic alterations modifying oncogene expression, and tumor microenvironment alterations [ 14 , 15 ].…”

“…The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor MDR has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades. Although relatively new alternatives in oncologic practice, the increased specificity and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as a promising prospect for the future of cancer management [ 15 , 16 ].…”

Anticancer potential of mebendazole against chronic myeloid leukemia: in silico and in vitro studies revealed new insights about the mechanism of action

“…TK inhibitors compete with ATP for the ATP binding site of the receptor, affecting protein phosphorylation and thus significantly reducing intracellular signaling and CML progress ( Rosti et al, 2017 ; Jiao et al, 2018 ). However, mutations in the ATP binding site leading to intrinsic and extrinsic mechanisms of drug resistance led to therapy failure, requiring the development of second and third generations of TKIs, such as nilotinib, dasatinib, bosutinib, and ponatinib to overcome the resistance in patients with CML ( Pophali and Patnaik, 2016 ; Machado et al, 2021 ). Therefore, it is imperative to develop studies seeking new molecules or redirect already known drugs to target the BCR-ABL protein with potential application in the CML.…”