Abstract
Chemoradiation, either alone or in combination with surgery or induction chemotherapy, is the current standard of care for most locally advanced solid tumors. Though chemoradiation is usually performed at the maximum tolerated doses of both chemotherapy and radiation, current cure rates are not satisfactory for many tumor entities, since tumor heterogeneity and plasticity result in chemo- and radioresistance. Advances in the understanding of tumor biology, a rapidly growing number of molecular targeting agents and novel technologies enabling the in-depth characterization of individual tumors, have fuelled the hope of entering an era of precision oncology, where each tumor will be treated according to its individual characteristics and weaknesses. At present though, molecular targeting approaches in combination with radiotherapy or chemoradiation have not yet proven to be beneficial over standard chemoradiation treatment in the clinical setting. A promising approach to improve efficacy is the combined usage of two targeting agents in order to inhibit backup pathways or achieve a more complete pathway inhibition. Here we review preclinical attempts to utilize such dual targeting strategies for future tumor radiosensitization.
Highlights
Chemoradiation is a current standard of care for the curative treatment of most locally advanced solid malignancies
A PubMed search based on the key words “agent∗, radiosensiti∗, radiotherapy, molecular targeted therapy, combined molecular targeting” was conducted and the results were screened for use of combined molecular targeting for radiosensitization in the preclinical setting
Molecular targeting approaches for tumor radiosensitization have been investigated for two decades [146,147,148,149], but their implementation into the clinic has proven extremely difficult
Summary
Chemoradiation is a current standard of care for the curative treatment of most locally advanced solid malignancies. Both modalities are generally administered at the maximum-tolerated doses to achieve best possible cure rates, which for many entities such as lung, brain, colorectal, bladder, or human Papillomavirus (HPV)-negative head and neck cancer, are still far from satisfactory. Combining radiotherapy with molecular targeting agents may offer an alternative to chemoradiation with potentially less severe side effects, provided the tumor cells are more dependent on the specific target than normal tissue. The combination was approved on the basis of the IMC 9815 phase III clinical trial, which demonstrated superiority over radiation alone in a range similar to the addition of cisplatin to radiotherapy [4]. Cetuximab-radiation was directly shown to be inferior to cisplatin-based chemoradiation in HPV-positive oropharyngeal cancer in two prospective phase III trials [9, 10] this entity had shown the greatest benefit from cetuximab in the IMC 9815 trial [11]
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