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Biological insights into effective and antagonistic combinations of targeted agents with chemotherapy in solid tumors

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Abstract

The potential for synergistic interactions between anticancer drugs has been used to justify combinations of agents in clinical trials. However, most combinations of targeted agents and chemotherapies have been tested in the clinic without previous systematic evaluation of their potential benefit. Preclinical studies may help in the identification of synergistic or antagonistic interactions. For antineoplastic therapies, these studies may reveal synergy or antagonism of the drug combinations. Synergy occurs when two agents given together produce higher antitumoral activity than the sum of each individual drug. This represents the ideal setting for the development of combinations of targeted agents and chemotherapies. On the other side, certain drug combinations have shown adverse results, indicative of an antagonistic effect. In this article, we review the preclinical molecular bases that justify approved combinations of targeted agents with chemotherapy including examples of synergistic and antagonistic combinations. We also discuss scenarios for rational associations of targeted agents based on biological data and propose strategies that may improve the success of combinations of anticancer agents.

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Authors and Affiliations

  1. Medical Oncology Department, Albacete University Hospital and AECC Unit, Albacete, Spain

    Alberto Ocaña

  2. Division of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Avenue, Toronto, ON, M5G 2M9, Canada

    Alberto Ocaña & Eitan Amir

  3. Durham Regional Cancer Centre, Oshawa, ON, Canada

    Orit Freedman

  4. Sector of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

    Bostjan Seruga

  5. Cancer Research Center, CSIC-University of Salamanca, Salamanca, Spain

    Atanasio Pandiella

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  1. Alberto Ocaña
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  2. Orit Freedman
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  4. Bostjan Seruga
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  5. Atanasio Pandiella
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Correspondence to Alberto Ocaña.

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Ocaña, A., Freedman, O., Amir, E. et al. Biological insights into effective and antagonistic combinations of targeted agents with chemotherapy in solid tumors. Cancer Metastasis Rev 33, 295–307 (2014). https://doi.org/10.1007/s10555-013-9451-7

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