Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome 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 p...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/6/1336 |
| _version_ | 1797541178866925568 |
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| author | Moritz Fürstenau Barbara Eichhorst |
| author_facet | Moritz Fürstenau Barbara Eichhorst |
| author_sort | Moritz Fürstenau |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T13:11:36Z |
| format | Article |
| id | doaj.art-5b1e3c13b89a41fcb71b4938a44305e7 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:11:36Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-5b1e3c13b89a41fcb71b4938a44305e72023-11-21T10:41:29ZengMDPI AGCancers2072-66942021-03-01136133610.3390/cancers13061336Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome ResistanceMoritz Fürstenau0Barbara Eichhorst1German CLL Study Group, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Department I of Internal Medicine, University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyGerman CLL Study Group, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD), Department I of Internal Medicine, University Hospital Cologne, University of Cologne, 50937 Cologne, GermanyThe 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.https://www.mdpi.com/2072-6694/13/6/1336chronic lymphocytic leukemiadrug resistancenovel agentscombination treatment |
| spellingShingle | Moritz Fürstenau Barbara Eichhorst Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance Cancers chronic lymphocytic leukemia drug resistance novel agents combination treatment |
| title | Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance |
| title_full | Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance |
| title_fullStr | Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance |
| title_full_unstemmed | Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance |
| title_short | Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance |
| title_sort | novel agents in chronic lymphocytic leukemia new combination therapies and strategies to overcome resistance |
| topic | chronic lymphocytic leukemia drug resistance novel agents combination treatment |
| url | https://www.mdpi.com/2072-6694/13/6/1336 |
| work_keys_str_mv | AT moritzfurstenau novelagentsinchroniclymphocyticleukemianewcombinationtherapiesandstrategiestoovercomeresistance AT barbaraeichhorst novelagentsinchroniclymphocyticleukemianewcombinationtherapiesandstrategiestoovercomeresistance |