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Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma

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Title: Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma
Authors: Yang, Zijian Browse this author
Suda, Goki Browse this author →KAKEN DB
Maehara, Osamu Browse this author
Ohara, Masatsugu Browse this author
Yoda, Tomoka Browse this author
Sasaki, Takashi Browse this author
Kohya, Risako Browse this author
Yoshida, Sonoe Browse this author
Hosoda, Shunichi Browse this author
Tokuchi, Yoshimasa Browse this author
Kitagataya, Takashi Browse this author
Suzuki, Kazuharu Browse this author
Kawagishi, Naoki Browse this author
Nakai, Masato Browse this author
Sho, Takuya Browse this author
Natsuizaka, Mitsuteru Browse this author
Ogawa, Koji Browse this author
Ohnishi, Shunsuke Browse this author
Sakamoto, Naoya Browse this author →KAKEN DB
Keywords: resistance
mechanism
immune checkpoint inhibitor
atezolizumab
bevacizumab
hepatocellular carcinoma
progressive disease
VEGF-D
angiopoietin-2
Issue Date: Feb-2023
Publisher: MDPI
Journal Title: Cancers
Volume: 15
Issue: 3
Start Page: 593
Publisher DOI: 10.3390/cancers15030593
Abstract: Simple Summary The possible mechanisms of resistance to atezolizumab/bevacizumab for unresectable HCC and the subsequent response to these therapies remain underexplored. The sequential changes in serum growth factors, including VEGF-A, VEGF-C, VEGF-D, ANG-2, FGF-19, HGF, and EGF during atezolizumab/bevacizumab for unresectable HCC were evaluated in 46 patients. Of 32 patients with disease control, 28 experienced PD after CR, PR, or SD with atezolizumab/bevacizumab. Growth factor changes between the baseline and best overall response points (BOR) for patients with disease control showed that FGF-19 significantly increased and ANG2 significantly decreased at the BOR. Growth factor changes between the BOR and the PD point in 28 patients who experienced PD after disease control showed that VEGF-D and ANG2 significantly increased at the PD point compared with that at the BOR. Summarily, increased serum VEGF-D and ANG-2 levels might contribute to developing resistance to atezolizumab/bevacizumab for unresectable HCC and might be target molecules in subsequent salvage therapies. The possible mechanisms of resistance to atezolizumab/bevacizumab for unresectable HCC, and the subsequent response to these therapies, remain underexplored. The sequential changes in serum growth factors, including VEGF-A, VEGF-C, VEGF-D, ANG-2, FGF-19, HGF, and EGF during atezolizumab/bevacizumab for unresectable HCC were evaluated in 46 patients. Patients who experienced PD after CR, PR, or SD to atezolizumab/bevacizumab were evaluated. A total of 4, 9, 19, and 14 patients showed CR, PR, SD, and PD, respectively. Of 32 patients with disease control, 28 experienced PD after CR, PR, or SD with atezolizumab/bevacizumab. Baseline growth factor levels were similar between patients with or without disease control and those with or without an objective response. Growth factor changes between the baseline and the best overall response points (BOR) for patients with disease control showed that FGF-19 significantly increased and ANG2 significantly decreased at the BOR. Growth factor changes between the BOR and the PD point in 28 patients who experienced PD after disease control showed that VEGF-D and ANG2 significantly increased at the PD point compared with that at the BOR. Summarily, increased serum VEGF-D and ANG-2 levels might contribute to developing resistance to atezolizumab/bevacizumab for unresectable HCC and might be target molecules in subsequent salvage therapies.
Type: article
URI: http://hdl.handle.net/2115/89182
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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