In Vitro Elucidation of Drug Combination Synergy in Treatment of Pancreatic Ductal Adenocarcinoma

被引:4
作者
Bush, Kevin T. [1 ,2 ]
Boichard, Amelie [3 ]
Tsigelny, Igor F. [1 ,4 ]
机构
[1] CureMatch Inc, 6440 Lusk Blvd,Suite D206, San Diego, CA 92121 USA
[2] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Ctr Personalized Med, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, San Diego Supercomp Ctr, La Jolla, CA 92093 USA
关键词
Pancreatic ductal adenocarcinoma; combination therapy; precision medicine; ALPHA-BISABOLOL; CANCER; IMPACT; SENSITIVITY; MANAGEMENT; MUTATIONS; MEDICINE; BIOLOGY; MODELS; KRAS;
D O I
10.21873/anticanres.12434
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background/Aim: Advances in therapies targeting proteins and pathways affected by genetic alterations has raised the possibility of personalized cancer treatments. Materials and Methods: The efficacy of targeting molecular aberrations was determined in the pancreatic ductal adenocarcinoma (PDAC) cell line, CAPAN2. Two mutations were targeted, KRAS (p.G12V) and ABL1 (p.G1060D), and cells were treated with regorafenib and trametinib, individually and in combination. Results: Exposure to either drug significantly increased cell death compared to the current standard of care, gemcitabine. Treatment with combinations of the drugs led to significant increases in cell death compared to either monotherapy. Strong additive/synergistic interactions were observed across a range of dosages and ratios, reducing dose requirements with potential clinical relevance. Conclusion: The data obtained in this PDAC cell model: i) support the use of matched monotherapies; ii) indicate the effectiveness of matched combination therapies; and iii) provide potential proof-of-concept for precision medicine approach to cancer treatment.
引用
收藏
页码:1967 / 1977
页数:11
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