Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F25%3A00082197" target="_blank" >RIV/65269705:_____/25:00082197 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/25:00141511

Výsledek na webu

<a href="https://www.nature.com/articles/s41375-025-02662-y" target="_blank" >https://www.nature.com/articles/s41375-025-02662-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41375-025-02662-y" target="_blank" >10.1038/s41375-025-02662-y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice

Popis výsledku v původním jazyce

The integration of BTK and BCL2 inhibitors into the treatment of patients with chronic lymphocytic leukemia (CLL) represents a paradigm shift and has led to significant improvements in clinical outcomes, including prolonged survival and enhanced quality of life. However, despite the efficacy of these agents, resistance to targeted therapy remains a major challenge, ultimately resulting in treatment failure and disease progression for a significant proportion of patients. Related to this, diagnostic testing for genetic variants associated with resistance, such as mutations in BTK, PLCG2 and BCL2, may become an increasingly common part of clinical routine practice. Addressing the need for placing the current knowledge in context, here we summarize the evidence from clinical studies and examine the underlying biology of both genetic and non-genetic resistance. Furthermore, we outline methodological approaches for the detection of gene alterations associated with targeted therapy resistance, discuss how to interpret these findings and highlight interpretation challenges. Finally, we offer insights into the clinical relevance of identifying genetic resistance to inform personalized treatment strategies and improve patient outcomes.

Název v anglickém jazyce

Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice

Popis výsledku anglicky

The integration of BTK and BCL2 inhibitors into the treatment of patients with chronic lymphocytic leukemia (CLL) represents a paradigm shift and has led to significant improvements in clinical outcomes, including prolonged survival and enhanced quality of life. However, despite the efficacy of these agents, resistance to targeted therapy remains a major challenge, ultimately resulting in treatment failure and disease progression for a significant proportion of patients. Related to this, diagnostic testing for genetic variants associated with resistance, such as mutations in BTK, PLCG2 and BCL2, may become an increasingly common part of clinical routine practice. Addressing the need for placing the current knowledge in context, here we summarize the evidence from clinical studies and examine the underlying biology of both genetic and non-genetic resistance. Furthermore, we outline methodological approaches for the detection of gene alterations associated with targeted therapy resistance, discuss how to interpret these findings and highlight interpretation challenges. Finally, we offer insights into the clinical relevance of identifying genetic resistance to inform personalized treatment strategies and improve patient outcomes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Leukemia

ISSN

0887-6924

e-ISSN

1476-5551

Svazek periodika

39

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

2049-2060

Kód UT WoS článku

001514279700001

EID výsledku v databázi Scopus

2-s2.0-105013590108