Non-small cell lung cancer (NSCLC) is the most prevalent type of
lung cancer, which is the leading cause of
cancer-related deaths worldwide. Over the past decades, tumour angiogenesis has been intensely studied in the treatment of NSCLC due to its fundamental role in
cancer progression. Several
anti-angiogenic drugs, such as recombinant
endostatin (RE), have been evaluated in several preclinical and clinical trials, with mixed and often disappointing results. However, there is currently an emerging interest in RE due to its ability to create a vascular normalization window, which could further improve treatment efficacy of the standard NSCLC treatment. This review provides an overview of preclinical and clinical studies that combined RE and
radiotherapy for NSCLC treatment. Furthermore, it highlights the ongoing challenges that have to be overcome in order to maximize the benefit; as well as the potential advantage of combinations with particle
therapy and
immunotherapy, which are rapidly gaining momentum in the treatment landscape of NSCLC. Different angiogenic and immunosuppressive effects are observed between particle
therapy and conventional X-ray
radiotherapy. The combination of RE, particle
therapy and
immunotherapy presents a promising future therapeutic triad for NSCLC.