Association of oncolytic adenoviruses with chemotherapies: an overview and future directions.
Oncolytic adenoviruses have been used in different preclinical and clinical studies, showing their capacity to kill tumor cells without major adverse events. However, these studies also underline the limitations of this approach. The efficacy of oncolytic adenoviruses is hampered by their limited ability to transduce some tumor types, their lack of selectivity, and their poor dissemination within tumors. In addition, the host immune response may limit oncolytic adenovirus efficacy. Combining oncolytic adenoviruses with chemotherapeutics constitutes an appealing strategy to increase their potency. The first part of this review describes the molecular basis of oncolytic adenoviruses, their use in preclinical studies and clinical trials, their limitations, and strategies to circumvent these limitations. The second part will focus on studies combining oncolytic adenoviruses with chemotherapeutic drugs, including standard chemotherapeutic drugs, molecularly targeted drugs, and other drugs that have been combined with oncolytic adenoviruses. Finally, based on these studies, we describe future directions and general rules that could be followed to identify chemotherapeutic drugs displaying additive/synergistic effects when combined with oncolytic adenoviruses.
CNRS UMR 8203, Vectorologie et thérapeutiques anti-cancéreuses, Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France; Univ Paris-Sud, 15 rue Georges Clémenceau, 91405 Orsay Cedex, France.
Christian
C
Bressy
CNRS UMR 8203, Vectorologie et thérapeutiques anti-cancéreuses, Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif Cedex, France; Univ Paris-Sud, 15 rue Georges Clémenceau, 91405 Orsay Cedex, France. Electronic address: benihoud@gustaveroussy.fr.
Karim
K
Benihoud
D000256:Adenoviridae / Q000235:genetics*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016679:Genome, Viral; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*
D000970:Antineoplastic Agents; D014764:Viral Proteins
CRAd; Chemotherapeutic; Oncolytic adenoviruses