Vinorelbine Augments Radiotherapy in Hepatocellular Carcinoma

• Published in: Cancers Vol. 12; no. 4; p. 872
• Main Authors: Yeoh, Kheng Wei, Prawira, Aldo, Saad, Muhammad Zafrie Bin, Lee, Kok Ming, Lee, Eric Ming Hon, Low, Gee Keng, Mohd Nasir, Mohamed Hakim Bin, Phua, Jun Hao, Chow, Wendy Wan Li, Lim, Iris Jiu Hia, Omar, Yusnita Binte, Ho, Rebecca Zhi Wen, Le, Thi Bich Uyen, Vu, Thanh Chung, Soo, Khee Chee, Huynh, Hung
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.04.2020; MDPI
• Subjects: Angiogenesis; Apoptosis; Cancer therapies; Cell cycle; Cell growth; Cell proliferation; Cell survival; Clinical trials; Deoxyribonucleic acid; DNA; DNA damage; DNA repair; Hepatocellular carcinoma; Investigations; Liver cancer; Medical prognosis; Radiation therapy; Toxicity; Tumors; Vinorelbine; Xenografts; vinorelbine; radiotherapy; cost-effectiveness; DNA repair; hepatocellular carcinoma; radio sensitization
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12040872

There is a need to improve the effectiveness of radiotherapy (RT) in hepatocellular carcinoma (HCC). Therefore, the purpose of this study was to explore the efficacy and toxicity of the anti-microtubule agent Vinorelbine as a radiosensitizer in HCC. The radio sensitivity of 16 HCC patient-derived xenograft (PDX) models was determined by quantifying the survival fraction following irradiation in vitro, and Vinorelbine radio sensitization was determined by clonogenic assay. Ectopic HCC xenografts were treated with a single dose of 8 Gy irradiation and twice-weekly 3 mg/kg Vinorelbine. Tumor growth and changes in the proteins involved in DNA repair, angiogenesis, tumor cell proliferation, and survival were assessed, and the 3/16 (18.75%), 7/16 (43.75%), and 6/16 (37.5%) HCC lines were classified as sensitive, moderately sensitive, and resistant, respectively. The combination of RT and Vinorelbine significantly inhibited tumor growth, DNA repair proteins, angiogenesis, and cell proliferation, and promoted more apoptosis compared with RT or Vinorelbine treatment alone. Vinorelbine improved HCC tumor response to standard irradiation with no increase in toxicity. HCC is prevalent in less developed parts of the world and is mostly unresectable on presentation. Vinorelbine and conventional radiotherapy are cost-effective, well-established modalities of cancer treatment that are readily available. Therefore, this strategy can potentially address an unmet clinical need, warranting further investigation in early-phase clinical trials.