2016
DOI: 10.1016/j.clon.2016.08.004
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The Challenges Faced in Developing Novel Drug Radiation Combinations in Non-small Cell Lung Cancer

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Cited by 6 publications
(7 citation statements)
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“…A promising strategy is to combine molecularly targeted drugs that act synergistically with RT with respect to tumour cell killing as an alternative to chemotherapy. If they do not result in excess normal tissue toxicity this could improve the therapeutic index of RT [15] , [16] . A key element to the success of such a strategy is to refine our understanding of the molecular mechanisms that mediate radioresistance to optimise the combination of molecularly targeted drugs and RT.…”
Section: Discussionmentioning
confidence: 99%
“…A promising strategy is to combine molecularly targeted drugs that act synergistically with RT with respect to tumour cell killing as an alternative to chemotherapy. If they do not result in excess normal tissue toxicity this could improve the therapeutic index of RT [15] , [16] . A key element to the success of such a strategy is to refine our understanding of the molecular mechanisms that mediate radioresistance to optimise the combination of molecularly targeted drugs and RT.…”
Section: Discussionmentioning
confidence: 99%
“…Beyond conventional radiation dose response and the impact of hypofractionation, there is a paucity of information on the effect of systemic therapy as a radiosensitizer in the treatment of mesothelioma. Beyond the classical combination of a cytotoxic agent with radiation, other potential combinations could include the combination of DNA damage repair agents or immune modulating agents with radiation as is being considered in other primary tumour sites (11). Certainly, there is a clear need to address the absence of pre-clinical and clinical data regarding the radiosensitivity of mesothelioma to either radiation alone or radiation in combination with systemic therapy.…”
Section: Is Mesothelioma An Inherently Radioresistant Cancer?mentioning
confidence: 99%
“…These pathways are actionable [15] , [16] , [17] , [18] : potent novel agents targeting DNA damage response pathways are becoming clinically available [19] and strategies for synergistic combination of systemic agents with RT are being realised across tumours [20] , [21] , [22] , [23] , [24] . Careful, efficient and multidisciplinary clinical trial design is essential for accurate assessment of the toxicities associated with these new and challenging treatment paradigms, and to ensure that the maximum impact on therapeutic index is achieved [25] , [26] .…”
Section: Introductionmentioning
confidence: 99%
“…The potential targets are extensively reviewed as radio-sensitisers in Chalmers et al [26] but are briefly summarised here. PARP (poly-ADP ribose polymerase) enzymes are involved not only in repair of single strand DNA breaks but are key regulators of DNA damage repair [29] .…”
Section: Introductionmentioning
confidence: 99%