Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY, 40536, USA.
Sci Rep. 2021 Feb 11;11(1):3528. doi: 10.1038/s41598-021-82318-w.
Microsomal prostaglandin E2 synthase 1 (mPGES-1) is recognized as a promising target for a next generation of anti-inflammatory drugs that are not expected to have the side effects of currently available anti-inflammatory drugs. Lapatinib, an FDA-approved drug for cancer treatment, has recently been identified as an mPGES-1 inhibitor. But the efficacy of lapatinib as an analgesic remains to be evaluated. In the present clinical data mining (CDM) study, we have collected and analyzed all lapatinib-related clinical data retrieved from clinicaltrials.gov. Our CDM utilized a meta-analysis protocol, but the clinical data analyzed were not limited to the primary and secondary outcomes of clinical trials, unlike conventional meta-analyses. All the pain-related data were used to determine the numbers and odd ratios (ORs) of various forms of pain in cancer patients with lapatinib treatment. The ORs, 95% confidence intervals, and P values for the differences in pain were calculated and the heterogeneous data across the trials were evaluated. For all forms of pain analyzed, the patients received lapatinib treatment have a reduced occurrence (OR 0.79; CI 0.70-0.89; P = 0.0002 for the overall effect). According to our CDM results, available clinical data for 12,765 patients enrolled in 20 randomized clinical trials indicate that lapatinib therapy is associated with a significant reduction in various forms of pain, including musculoskeletal pain, bone pain, headache, arthralgia, and pain in extremity, in cancer patients. Our CDM results have demonstrated the significant analgesic effects of lapatinib, suggesting that lapatinib may be repurposed as a novel type of analgesic.
微粒体前列腺素 E2 合酶 1（mPGES-1）被认为是新一代抗炎药物的有希望的靶点，预计这些药物不会产生现有抗炎药物的副作用。拉帕替尼是一种已获 FDA 批准用于癌症治疗的药物，最近被确定为 mPGES-1 抑制剂。但是，拉帕替尼作为一种镇痛药的疗效仍有待评估。在本临床数据挖掘（CDM）研究中，我们收集并分析了从 clinicaltrials.gov 检索到的所有与拉帕替尼相关的临床数据。我们的 CDM 利用了荟萃分析方案，但与传统的荟萃分析不同，所分析的临床数据不仅限于临床试验的主要和次要结局。所有与疼痛相关的数据都用于确定接受拉帕替尼治疗的癌症患者中各种形式疼痛的数量和比值比（OR）。计算了疼痛差异的 OR、95%置信区间和 P 值，并评估了试验间的异质性数据。对于分析的所有形式的疼痛，接受拉帕替尼治疗的患者疼痛发生的频率降低（OR 0.79；CI 0.70-0.89；P = 0.0002 表示整体效果）。根据我们的 CDM 结果，在 20 项随机临床试验中招募的 12765 名患者的可用临床数据表明，拉帕替尼治疗与癌症患者各种形式的疼痛（包括肌肉骨骼疼痛、骨痛、头痛、关节痛和四肢疼痛）的显著减轻相关。我们的 CDM 结果表明拉帕替尼具有显著的镇痛作用，提示拉帕替尼可能被重新用作一种新型的镇痛药。
