The molecular basis of the chemosensitivity of metastatic cutaneous melanoma to chemotherapy

Parker, Katharine A.; Glaysher, Sharon; Polak, Marta E.; Gabriel, Francis G.; Johnson, Penny; Knight, Louise A.; Poole, Matthew; Narayanan, Ajit; Hurren, Jeremy; Cree, Ian A.

doi:10.1136/jcp.2010.080119

Cited by 24 publications

(22 citation statements)

References 23 publications

(29 reference statements)

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“…In present study, the availability of esophageal cancer samples using the ATP-TCA was 90.5%, which is similar to the evaluability rates achieved in other 'cleaner' tumor types using this assay [27,28] . Other in vitro studies of esophageal cancer cells, including the use of the MTT assay and histoculture drug response assay, have produced similar evaluability rates [29,30] .…”

Section: Discussionsupporting

confidence: 65%

“…Other in vitro studies of esophageal cancer cells, including the use of the MTT assay and histoculture drug response assay, have produced similar evaluability rates [29,30] . The ATP-TCA has been shown to be more sensitive than these assays, and to have technical advantages over the MTT and clonogenic assays [27][28][29][30] . Previous studies with the ATP-TCA suggested that the assay was a good model for the investigation of tumor chemosensitivity and the results so far showed good correlation with clinical trial results in ovarian cancer [18,31] .…”

Section: Discussionmentioning

confidence: 99%

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Heterogeneity of chemosensitivity in esophageal cancer using ATP-tumor chemosensitivity assay

Ling

et al. 2012

Acta Pharmacol Sin

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Aim: Current chemotherapy for esophageal cancer is conducted on the basis of empirical information from clinical trials, which fails to take into account the known heterogeneity of chemosensitivity between patients. This study was aimed to demonstrate the degree of heterogeneity of chemosensitivity in esophageal cancers. Methods: A total of 42 esophageal cancer specimens were collected. The heterogeneity of chemosensitivity in esophageal cancer specimens was examined using an ex vivo ATP-tumor chemosensitivity assay (ATP-TCA). Results: Thirty eight specimens produced evaluable results (90.5%). The most active single agent tested was nedaplatin, to which 28.9% of samples were sensitive. Combinations of chemotherapy agents exhibited much higher sensitivity: cisplatin+paclitaxel was sensitive in 16 of 38 (42.1%) of samples, while nedaplatin+paclitaxel was more effective, which was sensitive in 20 of 38 cases (52.6%). Conclusion: There was a marked heterogeneity of chemosensitivity in esophageal cancer. Chemosensitivity testing may provide a practical method for testing new regimens before clinical trials in esophageal cancer patients.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Heterogeneity of chemosensitivity in esophageal cancer using ATP-tumor chemosensitivity assay

Ling

et al. 2012

Acta Pharmacol Sin

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“…8). This is an important advantage because the tumor tissue amount needed for the ATP assay limits the clinical use for certain tumor entities with a low tumor volume like primary melanoma tumors (24). In addition, the dissociation and isolation of cells from tumor tissue can lead up to 75 % of damaged cells (8) and, therefore, introducing the risk of selection of certain tumor or nontumor cells while eliminating others.…”

Section: Discussionmentioning

confidence: 99%

“…In general, we applied at least six concentrations ranging from 0.03 to 1,000 mmol/L. The concentration range was adapted for each chemotherapeutic based on prior evaluations for in vitro chemosensitivity assays (22)(23)(24) as well as our own preliminary investigations on tumor cell line-derived spheroid cultures (19). For each tumor biopsy, we performed immunocytochemical characterization (Fig.…”

Section: Tmf-based Determination Of Chemosensitivity Patternmentioning

confidence: 99%

Direct Chemosensitivity Monitoring Ex Vivo on Undissociated Melanoma Tumor Tissue by Impedance Spectroscopy

Jahnke¹,

Poenick²,

Maschke

et al. 2014

Cancer Research

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Stage III/IV melanoma remains incurable in most cases due to chemotherapeutic resistance. Thus, predicting and monitoring chemotherapeutic responses in this setting offer great interest. To overcome limitations of existing assays in evaluating the chemosensitivity of dissociated tumor cells, we developed a label-free monitoring system to directly analyze the chemosensitivity of undissociated tumor tissue. Using a preparation of tumor micro-fragments (TMF) established from melanoma biopsies, we characterized the tissue organization and biomarker expression by immunocytochemistry. Robust generation of TMF was established successfully and demonstrated on a broad range of primary melanoma tumors and tumor metastases. Organization and biomarker expression within the TMF were highly comparable with tumor tissue, in contrast to dissociated, cultivated tumor cells. Using isolated TMF, sensitivity to six clinically relevant chemotherapeutic drugs (dacarbazine, doxorubicin, paclitaxel, cisplatin, gemcitabine, and treosulfan) was determined by impedance spectroscopy in combination with a unique microcavity array technology we developed. In parallel, comparative analyses were performed on monolayer tumor cell cultures. Lastly, we determined the efficacy of chemotherapeutic agents on TMF by impedance spectroscopy to obtain individual chemosensitivity patterns. Our results demonstrated nonpredictable differences in the reaction of tumor cells to chemotherapy in TMF by comparison with dissociated, cultivated tumor cells. Our direct impedimetric analysis of melanoma biopsies offers a direct ex vivo system to more reliably predict patient-specific chemosensitivity patterns and to monitor antitumor efficacy. Cancer Res; 74(22); 6408-18. Ó2014 AACR.

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“…We have used the Taqman Array (Life Technologies) to assess the expression of 92 genes implicated in resistance to anticancer agents by qRT-PCR in a number of tumour types (23)(24)(25). This required just two 1 mm punches from FFPE tumour blocks.…”

Section: Mechanisms Of Anticancer Drug Resistancementioning

confidence: 99%

Designing personalised cancer treatments

Cree

2013

Journal of Controlled Release

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The concept of personalized medicine for cancer is not new. It arguably began with the attempts by Salmon and Hamburger to produce a viable cellular chemosensitivity assay in the 1970s, and continues to this day. While clonogenic assays soon fell out of favour due to their high failure rate, other cellular assays fared better and although they have not entered widespread clinical practice, they have proved to be very useful research tools. For instance, the ATP-based chemosensitivity assay was developed in the early 1990s and is highly standardised. It has proved useful for evaluating new drugs and combinations, and in recent years has been used to understand the molecular basis of drug resistance and sensitivity to anti-cancer drugs.Recent developments allow unparalleled genotyping and phenotyping of tumours, providing a plethora of targets for the development of new cancer treatments. However, validation of such targets and new agents to permit translation to the clinic remains difficult. There has been one major disappointment in that cell lines, though useful, do not often reflect the behaviour of their parent cancers with sufficient fidelity to be useful. Low passage cell lines -either in culture or xenografts are being used to overcome some of these issues, but have several problems of their own. Primary cell culture remains useful, but large tumours are likely to receive neo-adjuvant treatment before removal and that limits the tumour types that can be studied. The development of new treatments remains difficult and prediction of the clinical efficacy of new treatments from pre-clinical data is as hard as ever. One lesson has certainly been that one cannot buck the biology -and that understanding the genome alone is not sufficient to guarantee success. Nowhere has this been more evident than in the development of EGFR inhibitors. Despite overexpression of EGFR by many tumour types, only those with activating EGFR mutations and an inability to circumvent EGFR blockade have proved susceptible to treatment.The challenge is how to use advanced molecular understanding with limited cellular assay information to improve both drug development and the design of companion diagnostics to guide their use. This has the capacity to remove much of the guesswork from the process and should improve success rates.

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The molecular basis of the chemosensitivity of metastatic cutaneous melanoma to chemotherapy

Cited by 24 publications

References 23 publications

Heterogeneity of chemosensitivity in esophageal cancer using ATP-tumor chemosensitivity assay

Heterogeneity of chemosensitivity in esophageal cancer using ATP-tumor chemosensitivity assay

Direct Chemosensitivity Monitoring Ex Vivo on Undissociated Melanoma Tumor Tissue by Impedance Spectroscopy

Designing personalised cancer treatments

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