Venniyoor Ajit
National Oncology Centre, The Royal Hospital, Muscat, Oman.
Med Hypotheses. 2021 Jan;146:110399. doi: 10.1016/j.mehy.2020.110399. Epub 2020 Nov 16.
Hepatocellular cancer (HCC) and renal cell cancer (RCC) are singularly resistant to conventional chemotherapy drugs but therapies targeting the supporting stroma have significantly altered their management. Two recent trials combining anti-angiogenic (AA) agents with immune checkpoint inhibitors (ICIs)- the IMbrave150 and IMmotion151 - have reported impressive progress over targeted agents. It has been suggested that bevacizumab, by improving tissue perfusion, changes the immune suppressive tumour microenvironment to an immune stimulatory one where the ICIs can be more effective. This hypothesis proposes an alternative explanation: That bevacizumab, by increasing tissue hypoxia, amplifies the mutational burden of the tumour by stress-induced mutagenesis, creating a hypermutator profile, which is more vulnerable to the ICI drug, atezolizumab. Additionally, ICIs are known to cause hyperprogression in some tumours, and bevacizumab could provide further benefit by starving these rapidly proliferative tumours of blood supply and nutrients.
肝细胞癌（HCC）和肾细胞癌（RCC）对传统化疗药物具有独特的耐药性，但针对支持性基质的疗法已显著改变了它们的治疗方式。最近两项将抗血管生成（AA）药物与免疫检查点抑制剂（ICI）联合使用的试验——IMbrave150和IMmotion151——报告称在靶向药物方面取得了令人瞩目的进展。有人认为，贝伐单抗通过改善组织灌注，将免疫抑制性肿瘤微环境转变为免疫刺激性微环境，使ICI在其中更有效。这一假设提出了另一种解释：贝伐单抗通过增加组织缺氧，通过应激诱导的诱变增加肿瘤的突变负担，形成高突变特征，这使得肿瘤对ICI药物阿替利珠单抗更敏感。此外，已知ICI会在某些肿瘤中导致肿瘤快速进展，而贝伐单抗可以通过切断这些快速增殖肿瘤的血液供应和营养来提供进一步的益处。
