Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL)
Bruton’s tyrosine kinase (BTK) plays a key role in the B-cell receptor (BCR) signaling pathway and confers anti-apoptotic and proliferative properties to malignant B-cells in chronic lymphocytic leukemia (CLL). Small molecule BTK inhibitors were designed to bind BTK’s active site and block downstrea...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-12-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/14/12/2182 |
| _version_ | 1797380901244502016 |
|---|---|
| author | Alexandra Chirino Skye Montoya Anita Safronenka Justin Taylor |
| author_facet | Alexandra Chirino Skye Montoya Anita Safronenka Justin Taylor |
| author_sort | Alexandra Chirino |
| collection | DOAJ |
| description | Bruton’s tyrosine kinase (BTK) plays a key role in the B-cell receptor (BCR) signaling pathway and confers anti-apoptotic and proliferative properties to malignant B-cells in chronic lymphocytic leukemia (CLL). Small molecule BTK inhibitors were designed to bind BTK’s active site and block downstream signaling. These drugs have now been used in the treatment of thousands of patients with CLL, the most common form of leukemia in the western hemisphere. However, adverse effects of early generations of BTK inhibitors and resistance to treatment have led to the development of newer, more selective and non-covalent BTK inhibitors. As the use of these newer generation BTK inhibitors has increased, novel BTK resistance mutations have come to light. This review aims to discuss previously known and novel BTK mutations, their mechanisms of resistance, and their relationship with patient treatment. Also discussed here are future studies that are needed to investigate the underlying cause allowing these mutations to occur and how they incite resistance. New treatments on the horizon that attempt to maneuver around these resistance mutations can be met with new resistance mutations, creating an unmet need for patients with CLL. Novel therapies and combinations that address all forms of resistance are discussed. |
| first_indexed | 2024-03-08T20:44:40Z |
| format | Article |
| id | doaj.art-4a7dd8d9ca5b4874b29ff9e691caf6e7 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-08T20:44:40Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-4a7dd8d9ca5b4874b29ff9e691caf6e72023-12-22T14:11:13ZengMDPI AGGenes2073-44252023-12-011412218210.3390/genes14122182Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL)Alexandra Chirino0Skye Montoya1Anita Safronenka2Justin Taylor3Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USASylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USASylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USASylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USABruton’s tyrosine kinase (BTK) plays a key role in the B-cell receptor (BCR) signaling pathway and confers anti-apoptotic and proliferative properties to malignant B-cells in chronic lymphocytic leukemia (CLL). Small molecule BTK inhibitors were designed to bind BTK’s active site and block downstream signaling. These drugs have now been used in the treatment of thousands of patients with CLL, the most common form of leukemia in the western hemisphere. However, adverse effects of early generations of BTK inhibitors and resistance to treatment have led to the development of newer, more selective and non-covalent BTK inhibitors. As the use of these newer generation BTK inhibitors has increased, novel BTK resistance mutations have come to light. This review aims to discuss previously known and novel BTK mutations, their mechanisms of resistance, and their relationship with patient treatment. Also discussed here are future studies that are needed to investigate the underlying cause allowing these mutations to occur and how they incite resistance. New treatments on the horizon that attempt to maneuver around these resistance mutations can be met with new resistance mutations, creating an unmet need for patients with CLL. Novel therapies and combinations that address all forms of resistance are discussed.https://www.mdpi.com/2073-4425/14/12/2182chronic lymphocytic leukemiaBruton’s tyrosine kinaseresistance mutationstargeted therapy |
| spellingShingle | Alexandra Chirino Skye Montoya Anita Safronenka Justin Taylor Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL) Genes chronic lymphocytic leukemia Bruton’s tyrosine kinase resistance mutations targeted therapy |
| title | Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL) |
| title_full | Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL) |
| title_fullStr | Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL) |
| title_full_unstemmed | Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL) |
| title_short | Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL) |
| title_sort | resisting the resistance navigating btk mutations in chronic lymphocytic leukemia cll |
| topic | chronic lymphocytic leukemia Bruton’s tyrosine kinase resistance mutations targeted therapy |
| url | https://www.mdpi.com/2073-4425/14/12/2182 |
| work_keys_str_mv | AT alexandrachirino resistingtheresistancenavigatingbtkmutationsinchroniclymphocyticleukemiacll AT skyemontoya resistingtheresistancenavigatingbtkmutationsinchroniclymphocyticleukemiacll AT anitasafronenka resistingtheresistancenavigatingbtkmutationsinchroniclymphocyticleukemiacll AT justintaylor resistingtheresistancenavigatingbtkmutationsinchroniclymphocyticleukemiacll |