Histoculture drug response assay for gefitinib in non-small-cell lung cancer

Yoshimasu, Tatsuya; Ohta, Fuminori; Oura, Shoji; Tamaki, Takeshi; Shimizu, Yukio; Naito, Koma; Kiyoi, Megumi; Hirai, Yoshimitsu; Kawago, Mitsumasa; Okamura, Yoshitaka

doi:10.1007/s11748-008-0332-x

Cited by 15 publications

(13 citation statements)

References 13 publications

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“…59,60,[68][69][70] The MTT endpoint assay was most widely adopted for clinical correlation, and was used to develop an empirical value for HDRA responses to chemotherapy regimens. [59][60][61]71,72 Typically, mean data from four treated tumour culture wells were determined by calculating the spectrophotometric absorbance of MTT solution for both drug-treated and control tissue and adjusted for tumour weight, generating an inhibition rate as follows: inhibition rate (%) = (1−mean OD/weight of treated well/ mean OD/weight of control well) × 100.…”

Section: Pde Culturesmentioning

confidence: 99%

Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery

et al. 2020

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Preclinical models that can accurately predict outcomes in the clinic are much sought after in the field of cancer drug discovery and development. Existing models such as organoids and patient-derived xenografts have many advantages, but they suffer from the drawback of not contextually preserving human tumour architecture. This is a particular problem for the preclinical testing of immunotherapies, as these agents require an intact tumour human-specific microenvironment for them to be effective. In this review, we explore the potential of patient-derived explants (PDEs) for fulfilling this need. PDEs involve the ex vivo culture of fragments of freshly resected human tumours that retain the histological features of original tumours. PDE methodology for anti-cancer drug testing has been in existence for many years, but the platform has not been widely adopted in translational research facilities, despite strong evidence for its clinical predictivity. By modifying PDE endpoint analysis to include the spatial profiling of key biomarkers by using multispectral imaging, we argue that PDEs offer many advantages, including the ability to correlate drug responses with tumour pathology, tumour heterogeneity and changes in the tumour microenvironment. As such, PDEs are a powerful model of choice for cancer drug and biomarker discovery programmes.

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Section: Pde Culturesmentioning

confidence: 99%

Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery

et al. 2020

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“…The histoculture drug response assay (HDRA), is another drug sensitivity test that uses a three dimensional collagen gel, and the dose-response curve of gefitinib for lung cancer was reported using this method. However, the investigation did not include correlating the EGFR mutation and effects of gefitinib [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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.

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“…The responses of breast cancer to several drugs in the HDRA were correlated to recurrence-free survival 34 , 35 . Lung cancer response to nine drugs in the HDRA was correlated to the presence or absence of smoking history 36 , 37 . The HDRA has been used as a platform for the validation of drugs developed for cholangio-carcinoma 38 .…”

Section: Discussionmentioning

confidence: 99%

The identification of candidate effective combination regimens for pancreatic cancer using the histoculture drug response assay

Jun

Park

Lee

et al. 2020

Sci Rep

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The prognosis for patients with pancreatic cancer is extremely poor, as they are resistant to first line chemotherapy. The long-term goal of this study was to identify effective combination chemotherapy for pancreatic cancer using pancreatic cancer surgical specimens in the histoculture drug response assay (HDRA) based on three-dimensional culture of tumour fragments, which maintains nature tumour histology in vitro. From 2015 to 2017, the HDRA was performed with tumour specimens from 52 pancreatic cancer patients from Asan Medical Hospital. First, combination drug regimens showed higher drug efficacy and less patient variation than single drugs. Initially, 5-Fluorouracil(5-FU)/Belotecan/Oxaliplatinum and Tegafur/Gimeracil (TS-1)/Oxaliplatinum/Irinotecan were found to be effective. Second, we were able to correlate the efficacy of some drugs with tumour stage. Third, when designing new combination regimens containing 5-FU or gemcitabine, we could identify more effective drug combinations. This is the first study to demonstrate usefulness of the HDRA for pancreatic cancer. Using this technique, we could identify novel candidate combination drug regimens that should be effective in treating pancreatic cancer.

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Histoculture drug response assay for gefitinib in non-small-cell lung cancer

Abstract: HDRA appears to be applicable for evaluating sensitivity to gefitinib in NSCLC. It provides a convenient method for predicting the response to gefitinib in patients with NSCLC whose fresh tumor specimens are available.

Cited by 15 publications

References 13 publications

Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery

Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery

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

The identification of candidate effective combination regimens for pancreatic cancer using the histoculture drug response assay

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