Chemotherapy Sensitivity and Resistance Assays: A Systematic Review

Samson, David J; Seidenfeld, Jerome; Ziegler, Kathleen M; Aronson, Naomi

doi:10.1200/jco.2004.04.077

Cited by 108 publications

(87 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Finally, those wells which contained no cells were labelled "2." Due to beamtime limitations, only a few clones (clones 4,5,6,8,12, and 13, in bold and highlighted in Table 1) which included resistant clones to both 50 and 100 nM, sensitive clones to 100 nM but resistant to 50 nM, and sensitive clones to 50 nM could be measured. Cell survival was assessed with the trypan blue exclusion method.…”

Section: Cell Cloningmentioning

confidence: 99%

“…There are several chemotherapy sensitivity/resistance assays such as gene expression profiling (2,3), in vitro clonogenic and proliferation assays, cell metabolic activity assays, molecular assays, in vivo tumor growth and survival assays, and in vivo imaging assays amongst other (4,5). However, it is not clear yet whether these assays can improve the outcome of patients with cancer (6,7) and, so far, the clinical application has proved difficult (5).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Study of gemcitabine‐sensitive/resistant cancer cells by cell cloning and synchrotron FTIR microspectroscopy

et al. 2014

View full text Add to dashboard Cite

Over the last few years, significant scientific insight on the effects of chemotherapy drugs at cellular level using synchrotron-based FTIR (S-FTIR) microspectroscopy has been obtained. The work carried out so far has identified spectral differences in cancer cells before and after the addition of drugs. However, this had to account for the following issues. First, chemotherapy agents cause both chemical and morphological changes in cells, the latter being responsible for changes in the spectral profile not correlated with biochemical characteristics. Second, as the work has been carried out in mixed populations of cells (resistant and sensitive), it is important to distinguish the spectral differences which are due to sensitivity/resistance to those due to cell morphology and/or cell mixture. Here, we successfully cloned resistant and sensitive lung cancer cells to a chemotherapy drug. This allowed us to study a more uniform population and, more important, allowed us to study sensitive and resistant cells prior to the addition of the drug with S-FTIR microscopy. Principal component analysis (PCA) did not detect major differences in resistant cells prior to and after adding the drug. However, PCA separated sensitive cells prior to and after the addition of the drug. This would indicate that the spectral differences between cells prior to and after adding a drug might reside on those more or less sensitive cells that have been able to remain alive when they were collected to be studied with S-FTIR microspectroscopy. This is a proof of concept and a feasibility study showing a methodology that opens a new way to identify the effects of drugs on more homogeneous cell populations using vibrational spectroscopy. V C 2014 International Society for Advancement of Cytometry

show abstract

Section: Cell Cloningmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Study of gemcitabine‐sensitive/resistant cancer cells by cell cloning and synchrotron FTIR microspectroscopy

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Currently, there are no grounds to prioritize which agents should be administered to a given patient with pancreatic cancer. Sensitive and resistance assays have addressed this issue but have largely failed as they are based on clonogenicity and/or proliferation indexes and require both acquiring large amounts of tissue and maintaining cell viability for extended periods (5,6). On the other hand, it is possible to elicit pharmacodynamic responses by briefly exposing small amounts of tumor cells to a drug, an approach termed ex vivo testing (7).…”

Section: Introductionmentioning

confidence: 99%

A Fine-Needle Aspirate–Based Vulnerability Assay Identifies Polo-Like Kinase 1 as a Mediator of Gemcitabine Resistance in Pancreatic Cancer

Jimeno

Rubio-Viqueira

Rajeshkumar

et al. 2010

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

This work aimed to discover targets for combination treatment with gemcitabine in pancreatic cancer. We selected 11 tumors from our live collection of freshly generated pancreatic cancer xenografts with known degrees of varying gemcitabine sensitivity. We briefly (6 h) exposed fine-needle aspiration material to control vehicle or gemcitabine (1 μmol/L) and compared the gene expression of the treated and untreated samples using a reverse transcription-PCR-based, customized low-density array with 45 target genes of therapeutic interest. The gene expression of the untreated sample (which can be considered a baseline/static readout) was not predictive of gemcitabine efficacy in these tumors. Altogether, the only gene that differentiated sensitive versus resistant cases was polo-like kinase 1 (Plk1), showing >50% downregulation in sensitive cases and no change in the resistant cases. Inhibition of Plk1 by either small interfering RNA gene knockdown or with the Plk1 pathway modulator (ON 01910.Na) synergized with gemcitabine in gemcitabine-refractory in vitro models providing mechanistic proof of concept. In vivo experiments in gemcitabine-resistant xenografts showed synergistic activity decreasing cell proliferation and tumor regressions. A quantitative gene expression-based vulnerability assay identified Plk1 as a relevant target dictating the susceptibility of pancreatic cancer to gemcitabine. Dynamic interrogation of cancer has the potential to provide key information about mechanisms of resistance and to enhance individualization of treatment. Mol Cancer Ther; 9(2); 311-8. ©2010 AACR.

show abstract

“…For these purposes, various in vitro chemosensitivity assays have been developed and tested in the preclinical and clinical setting, predominantly in ovarian, breast, and lung cancer (15,16). Although the majority of older technologies like, e.g., tumor clonogenic assays and […”

mentioning

confidence: 99%

“…3 H]thymidine incorporation quantified drug sensitivity by growth inhibition of tumor cells, newer approaches like, e.g., the differential staining assay and the ATP bioluminescence assay (ATP-TCA) use the rate of tumor cell death as a readout (16). These latter assays take advantage of the quantification of cell viability as measures of anticancer drug effectiveness, whereas growth inhibition assays often promote single clones, thus failing to reflect the in vivo situation (15,17).…”

mentioning

confidence: 99%

In vitro Drug Sensitivity Predicts Response and Survival after Individualized Sensitivity-Directed Chemotherapy in Metastatic Melanoma: A Multicenter Phase II Trial of the Dermatologic Cooperative Oncology Group

Ugurel

Schadendorf

Pföhler

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct association between in vitro and in vivo chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between in vitro sensitivity and therapy outcome. Patients and Methods: The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free survival.Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five drug combinations using an ATP-based luminescence viability assay. Results: Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all study end points (per protocol). The drug combinations used were gemcitabine + treosulfan, paclitaxel + cisplatin, paclitaxel + doxorubicin, and gemcitabine + cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and 31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients compared with 16.1% in chemoresistant patients (P = 0.114); progression arrest (complete response + partial response + stable disease) was 59.1% versus 22.6% (P = 0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant patients (P = 0.041). Conclusion: In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome of melanoma patients treated with a sensitivitydirected chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.Melanoma is a cutaneous neoplasm known for its high aggressiveness, its early dissemination of metastases, and its poor prognosis once metastasized. Chemotherapy with dacarbacine (DTIC) does actually apply as the standard treatment regimen in metastasized melanoma, with reported response rates of only 10% to 18% (1). Even these might be overestimated, as recent studies using new standardized evaluation criteria (2) revealed much lower response rates of 6% to 7% (3, 4). This poor outcome does not rely on an impaired penetration of chemotherapeutics into the tumor, but has been proposed to be caused by chemoresistance mechanisms intrinsic to melanoma cells (5, 6). Moreover, biochemotherapy and immunotherapy regimens did not prove to be superior to DTIC (1, 7).Due to this unfavorable situation, a number of nonstandard chemotherapeutics were tested in small pilot studies to prove a stronger efficacy in melanoma. Although complete remissions of metastatic lesions could only be observed in few patients

show abstract

Chemotherapy Sensitivity and Resistance Assays: A Systematic Review

Cited by 108 publications

References 14 publications

Study of gemcitabine‐sensitive/resistant cancer cells by cell cloning and synchrotron FTIR microspectroscopy

Study of gemcitabine‐sensitive/resistant cancer cells by cell cloning and synchrotron FTIR microspectroscopy

A Fine-Needle Aspirate–Based Vulnerability Assay Identifies Polo-Like Kinase 1 as a Mediator of Gemcitabine Resistance in Pancreatic Cancer

In vitro Drug Sensitivity Predicts Response and Survival after Individualized Sensitivity-Directed Chemotherapy in Metastatic Melanoma: A Multicenter Phase II Trial of the Dermatologic Cooperative Oncology Group

Contact Info

Product

Resources

About