TY - JOUR
T1 - Arrest and Attack
T2 - Microtubule-Targeting Agents and Oncolytic Viruses Employ Complementary Mechanisms to Enhance Anti-Tumor Therapy Efficacy
AU - De, Sucheta
AU - Ehrlich, Marcelo
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/9
Y1 - 2024/9
N2 - Oncolytic viruses (OVs) are promising cancer immunotherapy agents that stimulate anti-tumor immunity through the preferential infection and killing of tumor cells. OVs are currently under limited clinical usage, due in part to their restricted efficacy as monotherapies. Current efforts for enhancement of the therapeutic potency of OVs involve their combination with other therapy modalities, aiming at the concomitant exploitation of complementary tumor weaknesses. In this context, microtubule-targeting agents (MTAs) pose as an enticing option, as they perturb microtubule dynamics and function, induce cell-cycle arrest, and cause mitotic cell death. MTAs induce therapeutic benefit through cancer-cell-autonomous and non-cell-autonomous mechanisms and are a main component of the standard of care for different malignancies. However, off-target effects and acquired resistance involving distinct cellular and molecular mechanisms may limit the overall efficacy of MTA-based therapy. When combined, OVs and MTAs may enhance therapeutic efficacy through increases in OV infection and immunogenic cell death and a decreased probability of acquired resistance. In this review, we introduce OVs and MTAs, describe molecular features of their activity in cancer cells, and discuss studies and clinical trials in which the combination has been tested.
AB - Oncolytic viruses (OVs) are promising cancer immunotherapy agents that stimulate anti-tumor immunity through the preferential infection and killing of tumor cells. OVs are currently under limited clinical usage, due in part to their restricted efficacy as monotherapies. Current efforts for enhancement of the therapeutic potency of OVs involve their combination with other therapy modalities, aiming at the concomitant exploitation of complementary tumor weaknesses. In this context, microtubule-targeting agents (MTAs) pose as an enticing option, as they perturb microtubule dynamics and function, induce cell-cycle arrest, and cause mitotic cell death. MTAs induce therapeutic benefit through cancer-cell-autonomous and non-cell-autonomous mechanisms and are a main component of the standard of care for different malignancies. However, off-target effects and acquired resistance involving distinct cellular and molecular mechanisms may limit the overall efficacy of MTA-based therapy. When combined, OVs and MTAs may enhance therapeutic efficacy through increases in OV infection and immunogenic cell death and a decreased probability of acquired resistance. In this review, we introduce OVs and MTAs, describe molecular features of their activity in cancer cells, and discuss studies and clinical trials in which the combination has been tested.
KW - JNK
KW - combination therapy
KW - microtubule-targeting agents
KW - oncolytic virus
UR - http://www.scopus.com/inward/record.url?scp=85204937199&partnerID=8YFLogxK
U2 - 10.3390/genes15091193
DO - 10.3390/genes15091193
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C2 - 39336785
AN - SCOPUS:85204937199
SN - 2073-4425
VL - 15
JO - Genes
JF - Genes
IS - 9
M1 - 1193
ER -