TY - JOUR
T1 - Moving Beyond the Standard of Care
T2 - Accelerate Testing of Radiation-Drug Combinations
AU - Lin, Steven H.
AU - Willers, Henning
AU - Krishnan, Sunil
AU - Sarkaria, Jann N.
AU - Baumann, Michael
AU - Lawrence, Theodore S.
N1 - Funding Information:
Disclosures: Within the past 36 months, all authors are supported by a U01 grant from the National Cancer Institute. S.H.L has received research funding from Beyond Spring Pharmaceuticals, STCube Pharmaceuticals, Nektar Pharmaceuticals, Hitachi Chemical Diagnostics, and Genentech; serves on advisory board for AstraZeneca, STCube Pharmaceuticals, and Beyond Spring Pharmaceuticals; and is a consultant for XRAD Therapeutics. J.N.S. has received research funding from GlaxoSmithKine, Curtana, Forma, AbbVie, Boehringer Ingelheim, Actuate, Bayer, Celgene, Cible, Wayshine, Boston Scientific, AstraZeneca, Black Diamond, and Karyopharm. M.B. has received funding for research projects and for educational grants to the University of Dresden by Bayer AG (2016-2018), Merck KGaA (2014-open), and Medipan (2014-2018); he is also on the supervisory board of HI-STEM (Heidelberg) for the German Cancer Research Center (DKFZ, Heidelberg) and is a member of the supervisory body of the Charité University Hospital, Berlin. As former chair of OncoRay (Dresden) and the current CEO and scientific chair of the German Cancer Research Center (DKFZ, Heidelberg), M.B. has been or is responsible for collaborations with a multitude of companies and institutions, worldwide; in this capacity, he has discussed potential projects and signed contracts for research funding and/or collaborations with industry and academia for his institute(s) and staff, including but not limited to pharmaceutical companies such as Bayer, Boehringer Ingelheim, Bosch, and Roche and other companies such as Siemens, IBA, Varian, Elekta, and Bruker. In this role, he was/is also responsible for the commercial technology transfer activities of his institute(s), including the creation of start-ups and licensing; this includes the DKFZ-PSMA617 related patent portfolio [WO2015055318 (A1), ANTIGEN (PSMA)] and similar IP portfolios.
Funding Information:
Disclosures: Within the past 36 months, all authors are supported by a U01 grant from the National Cancer Institute. S.H.L has received research funding from Beyond Spring Pharmaceuticals, STCube Pharmaceuticals, Nektar Pharmaceuticals, Hitachi Chemical Diagnostics, and Genentech; serves on advisory board for AstraZeneca, STCube Pharmaceuticals, and Beyond Spring Pharmaceuticals; and is a consultant for XRAD Therapeutics. J.N.S. has received research funding from GlaxoSmithKine, Curtana, Forma, AbbVie, Boehringer Ingelheim, Actuate, Bayer, Celgene, Cible, Wayshine, Boston Scientific, AstraZeneca, Black Diamond, and Karyopharm. M.B. has received funding for research projects and for educational grants to the University of Dresden by Bayer AG (2016-2018), Merck KGaA (2014-open), and Medipan (2014-2018); he is also on the supervisory board of HI-STEM (Heidelberg) for the German Cancer Research Center (DKFZ, Heidelberg) and is a member of the supervisory body of the Charité University Hospital, Berlin. As former chair of OncoRay (Dresden) and the current CEO and scientific chair of the German Cancer Research Center (DKFZ, Heidelberg), M.B. has been or is responsible for collaborations with a multitude of companies and institutions, worldwide; in this capacity, he has discussed potential projects and signed contracts for research funding and/or collaborations with industry and academia for his institute(s) and staff, including but not limited to pharmaceutical companies such as Bayer, Boehringer Ingelheim, Bosch, and Roche and other companies such as Siemens, IBA, Varian, Elekta, and Bruker. In this role, he was/is also responsible for the commercial technology transfer activities of his institute(s), including the creation of start-ups and licensing; this includes the DKFZ-PSMA617 related patent portfolio [WO2015055318 (A1), ANTIGEN (PSMA)] and similar IP portfolios.
Funding Information:
This research is supported in part by National Cancer Institute U01CA216468.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Radiation therapy is a major treatment modality used in > 60% of cancer patients as definitive local treatment for inoperable locoregionally confined tumors and as palliative therapy. Although cytotoxic chemotherapy enhances the effectiveness of treatment, the benefit over radiation therapy alone is modest. There is a need to enhance the effectiveness of local tumor control over what sequentially or concurrently administered cytotoxic chemotherapy provides. Although many biological pathways are known to enhance the effectiveness of radiation therapy, there is currently a paucity of drugs approved for use in combination. Several clinical trials have tested the effectiveness of combining targeted agents or immunotherapies with radiation therapy, but the results of these trials have been negative, likely stemming from the relative lack of preclinical evidence using appropriate experimental standardization or model systems. Accelerating the identification of agents tested in an appropriate clinical context and experimental systems or models would greatly enhance the potential to bring forward early testing of drugs that would not only be safe but also more effective. This article provides an overview of the opportunities and challenges of developing therapeutics to combine with radiation therapy, and some guidance toward preclinical and early clinical testing to improve the chance that advanced phase testing of drug-radiation combinations would be successful in the long term.
AB - Radiation therapy is a major treatment modality used in > 60% of cancer patients as definitive local treatment for inoperable locoregionally confined tumors and as palliative therapy. Although cytotoxic chemotherapy enhances the effectiveness of treatment, the benefit over radiation therapy alone is modest. There is a need to enhance the effectiveness of local tumor control over what sequentially or concurrently administered cytotoxic chemotherapy provides. Although many biological pathways are known to enhance the effectiveness of radiation therapy, there is currently a paucity of drugs approved for use in combination. Several clinical trials have tested the effectiveness of combining targeted agents or immunotherapies with radiation therapy, but the results of these trials have been negative, likely stemming from the relative lack of preclinical evidence using appropriate experimental standardization or model systems. Accelerating the identification of agents tested in an appropriate clinical context and experimental systems or models would greatly enhance the potential to bring forward early testing of drugs that would not only be safe but also more effective. This article provides an overview of the opportunities and challenges of developing therapeutics to combine with radiation therapy, and some guidance toward preclinical and early clinical testing to improve the chance that advanced phase testing of drug-radiation combinations would be successful in the long term.
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U2 - 10.1016/j.ijrobp.2021.08.018
DO - 10.1016/j.ijrobp.2021.08.018
M3 - Article
C2 - 34454045
AN - SCOPUS:85116550105
SN - 0360-3016
VL - 111
SP - 1131
EP - 1139
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 5
ER -