TY - JOUR
T1 - TAM kinase inhibition and immune checkpoint blockade– a winning combination in cancer treatment?
AU - Msaouel, Pavlos
AU - Genovese, Giannicola
AU - Gao, Jianjun
AU - Sen, Suvajit
AU - Tannir, Nizar M.
N1 - Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - Introduction: Immune checkpoint inhibitors (ICI) have shown great promise in a wide spectrum of malignancies. However, responses are not always durable, and this mode of treatment is only effective in a subset of patients. As such, there exists an unmet need for novel approaches to bolster ICI efficacy. Areas covered: We review the role of the Tyro3, Axl, and Mer (TAM) receptor tyrosine kinases in promoting tumor-induced immune suppression and discuss the benefits that may be derived from combining ICI with TAM kinase-targeted tyrosine kinase inhibitors. We searched the MEDLINE Public Library of Medicine (PubMed) and EMBASE databases and referred to ClinicalTrials.gov for relevant ongoing studies. Expert opinion: Targeting of TAM kinases may improve the efficacy of immune checkpoint blockade. However, it remains to be determined whether this effect will be better achieved by the selective targeting of each TAM receptor, depending on the context, or by multi-receptor TAM inhibitors. Triple inhibition of all TAM receptors is more likely to be associated with an increased risk for adverse events. Clinical trial designs should use high-resolution clinical endpoints and proper control arms to determine the synergistic effects of combining TAM inhibition with immune checkpoint blockade.
AB - Introduction: Immune checkpoint inhibitors (ICI) have shown great promise in a wide spectrum of malignancies. However, responses are not always durable, and this mode of treatment is only effective in a subset of patients. As such, there exists an unmet need for novel approaches to bolster ICI efficacy. Areas covered: We review the role of the Tyro3, Axl, and Mer (TAM) receptor tyrosine kinases in promoting tumor-induced immune suppression and discuss the benefits that may be derived from combining ICI with TAM kinase-targeted tyrosine kinase inhibitors. We searched the MEDLINE Public Library of Medicine (PubMed) and EMBASE databases and referred to ClinicalTrials.gov for relevant ongoing studies. Expert opinion: Targeting of TAM kinases may improve the efficacy of immune checkpoint blockade. However, it remains to be determined whether this effect will be better achieved by the selective targeting of each TAM receptor, depending on the context, or by multi-receptor TAM inhibitors. Triple inhibition of all TAM receptors is more likely to be associated with an increased risk for adverse events. Clinical trial designs should use high-resolution clinical endpoints and proper control arms to determine the synergistic effects of combining TAM inhibition with immune checkpoint blockade.
KW - TAM kinase inhibitors
KW - cabozantinib
KW - combination therapy
KW - immune checkpoint inhibitors
KW - sitravatinib
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U2 - 10.1080/14728222.2021.1869212
DO - 10.1080/14728222.2021.1869212
M3 - Review article
C2 - 33356674
AN - SCOPUS:85098623385
SN - 1472-8222
VL - 25
SP - 141
EP - 151
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
IS - 2
ER -