Universität zu Köln

Fuerstenau, Moritz and Eichhorst, Barbara (2021). Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance. Cancers, 13 (6). BASEL: MDPI. ISSN 2072-6694

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Abstract

Simple Summary Nowadays, many patients with chronic lymphocytic leukemia (CLL) are treated with so-called novel agents, including BTK inhibitors, Bcl-2 inhibitors and PI3K inhibitors. As CLL is a chronic disease, most patients will relapse on or after treatment with these drugs and various mechanisms behind this resistance to novel agents have been described. In this review, we present the current evidence on resistance to novel agents, discuss approaches to prevent its development and provide guidance on the treatment of patients who have already acquired resistance. The approval of Bruton's tyrosine kinase (BTK) inhibitors such as ibrutinib and acalabrutinib and the Bcl-2 inhibitor venetoclax have revolutionized the treatment of chronic lymphocytic leukemia (CLL). While these novel agents alone or in combination induce long lasting and deep remissions in most patients with CLL, their use may be associated with the development of clinical resistance. In this review, we elucidate the genetic basis of acquired resistance to BTK and Bcl-2 inhibition and present evidence on resistance mechanisms that are not linked to single genomic alterations affecting these target proteins. Strategies to prevent resistance to novel agents are discussed in this review with a special focus on new combination therapies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fuerstenau, Moritz UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichhorst, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-567395
DOI:	10.3390/cancers13061336
Journal or Publication Title:	Cancers
Volume:	13
Number:	6
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/56739