TY - JOUR
T1 - Therapeutic approaches and drug-resistance in chronic lymphocytic leukaemia
AU - Fatima, Narjis
AU - Crassini, Kyle R.
AU - Thurgood, Lauren
AU - Shen, Yandong
AU - Christopherson, Richard I.
AU - Kuss, Bryone
AU - Mulligan, Stephen P.
AU - Best, Oliver Giles
PY - 2020
Y1 - 2020
N2 - The treatment of chronic lymphocytic leukaemia has been revolutionised in recent years, first by the introduction of chemoimmunotherapy regimens and subsequently by the development of drugs, including ibrutinib, idelalisib and venetoclax, that target components of the B-cell receptor signalling pathway or B-cell lymphoma 2 family of proteins. Despite high initial response rates in patients treated with chemoimmunotherapy or targeted agents, a significant proportion of patients relapse with progressive and refractory disease. In a subset of these patients, drug resistance has been associated with specific genetic lesions or activation of alternate pro-survival pathways. However, the mechanisms that confer drug resistance in the remainder of the patients with refractory disease have yet to be fully elucidated. In this review, we discuss our current understanding of the mechanics of drug resistance in chronic lymphocytic leukaemia and describe how this knowledge may aid in rationalising future treatment strategies to prevent the development of refractory or aggressive transformation of the disease.
AB - The treatment of chronic lymphocytic leukaemia has been revolutionised in recent years, first by the introduction of chemoimmunotherapy regimens and subsequently by the development of drugs, including ibrutinib, idelalisib and venetoclax, that target components of the B-cell receptor signalling pathway or B-cell lymphoma 2 family of proteins. Despite high initial response rates in patients treated with chemoimmunotherapy or targeted agents, a significant proportion of patients relapse with progressive and refractory disease. In a subset of these patients, drug resistance has been associated with specific genetic lesions or activation of alternate pro-survival pathways. However, the mechanisms that confer drug resistance in the remainder of the patients with refractory disease have yet to be fully elucidated. In this review, we discuss our current understanding of the mechanics of drug resistance in chronic lymphocytic leukaemia and describe how this knowledge may aid in rationalising future treatment strategies to prevent the development of refractory or aggressive transformation of the disease.
KW - Chronic lymphocytic leukaemia
KW - Drug resistance
KW - Targeted cancer therapy
UR - http://www.scopus.com/inward/record.url?scp=85107443965&partnerID=8YFLogxK
U2 - 10.20517/cdr.2019.111
DO - 10.20517/cdr.2019.111
M3 - Review article
AN - SCOPUS:85107443965
VL - 3
SP - 532
EP - 549
JO - Cancer Drug Resistance
JF - Cancer Drug Resistance
SN - 2578-532X
IS - 3
ER -