In Vitro Drug Sensitivity Tests to Predict Molecular Target Drug Responses in Surgically Resected Lung Cancer

Abstract

BackgroundEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase (ALK) inhibitors have dramatically changed the strategy of medical treatment of lung cancer. Patients should be screened for the presence of the EGFR mutation or echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene prior to chemotherapy to predict their clinical response. The succinate dehydrogenase inhibition (SDI) test and collagen gel droplet embedded culture drug sensitivity test (CD-DST) are established in vitro drug sensitivity tests, which may predict the sensitivity of patients to cytotoxic anticancer drugs. We applied in vitro drug sensitivity tests for cyclopedic prediction of clinical responses to different molecular targeting drugs.MethodsThe growth inhibitory effects of erlotinib and crizotinib were confirmed for lung cancer cell lines using SDI and CD-DST. The sensitivity of 35 cases of surgically resected lung cancer to erlotinib was examined using SDI or CD-DST, and compared with EGFR mutation status.ResultsHCC827 (Exon19: E746-A750 del) and H3122 (EML4-ALK) cells were inhibited by lower concentrations of erlotinib and crizotinib, respectively than A549, H460, and H1975 (L858R+T790M) cells were. The viability of the surgically resected lung cancer was 60.0 ± 9.8 and 86.8 ± 13.9% in EGFR-mutants vs. wild types in the SDI (p = 0.0003). The cell viability was 33.5 ± 21.2 and 79.0 ± 18.6% in EGFR mutants vs. wild-type cases (p = 0.026) in CD-DST.ConclusionsIn vitro drug sensitivity evaluated by either SDI or CD-DST correlated with EGFR gene status. Therefore, SDI and CD-DST may be useful predictors of potential clinical responses to the molecular anticancer drugs, cyclopedically.

Chemical Profiling of Primary Mesothelioma Cultures Defines Subtypes with Different Expression Profiles and Clinical Responses

“…Therefore, we "chemically" profiled primary mesothelioma cultures with common chemotherapeutic drugs and subsequently treated 10 patients with the most effective drug or drug combination. This strategy has previously been successfully applied in lung cancer (36)(37)(38), ovarian cancer (39,40), and breast cancer (41) and showed that in vitro drug responsiveness bears clinically relevant information for patient treatment efficacy.…”

Vacquinol‑1 induces apoptosis in hepatocellular carcinoma cell

“…The average IC50 of these 10 individuals at 24, 48 and 72 h were 10.7, 8.9, 7.4 µM, respectively. The sensitivities of these cells to Vacq were further assessed by collagen gel droplet embedded CD-DST, an in vitro anticancer drug sensitivity test in which the reported clinical correlation was approximately 91% in several solid cancers (10,11). Patient-derived HCC cells were packaged into the collagen droplets to provide a 3-D culture environment and treated with Vacq at 15 µM for 24 h. Viable cells were deeply stained by neural red which presented in dark color in Fig.…”

The methods of in vitro selection of chemotherapeutic druds for individual chemotherapy of maligant tumors in patinets

“…Ряд иных способов опирается на такие критерии как активность ацетилхолинэстеразы, люцеферазы, топоизомеразы-II или секрецию лактатдегидрогеназы, ацетилхолинэстеразы, сукцинатдегидрогеназы и др. [28,40].…”

“…Он способен количественно оценивать чувствительность клеток из биопсийных образцов к противоопухолевым препаратам без контаминации культур фибробластами (табл. 1) [17,40,59,60,61]. Исследователи из университета Сиги (Япония), используя метод CD-DST, определили скорость ответа на терапию (RR), PFS и OS у 38 пациентов с колоректальным раком (grade IV).…”