A molecular 'signature' of primary breast cancer cultures; patterns resembling tumor tissue

Dairkee, Shanaz H.; Ji, Youngran; Ben, Yong; Moore, Dan H.; Meng, Zhenhang; Jeffrey, Stefanie S.

doi:10.1186/1471-2164-5-47

Cited by 55 publications

(32 citation statements)

References 22 publications

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“…The majority of arguments against the use of cultured cells to investigate tumor biology are based on the marked differences seen in the expression profiling of cultured cancer cells compared directly with tumor tissue (Perou et al , 1999; Ross et al , 2000; Welsh et al , 2001; Dairkee et al , 2004). Few examples exist where normal cells are included in such analysis and in these cases, expression profiles in culture, as would be expected from disparate environments, cluster separately from tissue (Perou et al , 1999).…”

Section: Discussionmentioning

confidence: 99%

Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma

Watt

Pourreyron

Purdie³

et al. 2011

Oncogene

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Identifying therapeutic targets for cancer treatment relies on consistent changes within particular types or sub-types of malignancy. The ability to define either consistent changes or sub-types of malignancy is often masked by tumor heterogeneity. To elucidate therapeutic targets in cutaneous squamous cell carcinoma (cSCC), the most frequent skin neoplasm with malignant potential, we have developed an integrated approach to gene expression profiling beginning with primary keratinocytes in culture. Candidate drivers of cSCC development were derived by first defining a set of in vitro cancer genes and then comparing their expression in a range of clinical data sets containing normal skin, cSCC and the benign hyper-proliferative condition psoriasis. A small interfering RNA (siRNA) screen of the resulting 21 upregulated genes has yielded targets capable of reducing xenograft tumor volume in vivo. Small-molecule inhibitors for one target, Polo-like kinase-1 (PLK1), are already in clinical trials for other malignancies, and our data show efficacy in cSCC. Another target, C20orf20, is identified as being overexpressed in cSCC, and siRNA-mediated knockdown induces apoptosis in vitro and reduces tumor growth in vivo. Thus, our approach has shown established and uncharacterized drivers of tumorigenesis with potent efficacy as therapeutic targets for the treatment of cSCC.

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Section: Discussionmentioning

confidence: 99%

Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma

Watt

Pourreyron

Purdie³

et al. 2011

Oncogene

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“…The generation of stable cell lines for functional testing from individual patients using traditional 2D cultivation on cell culture dishes in typical media is laborious and generally unsuccessful. Such homogeneous cell lines typically have properties that are distinct from the parental tumour, at both the genotypic level (for example, mutations and expression profiles) 27,28 and phenotypic level (much more rapid growth and increased sensitivity to chemotherapies); in particular, these lines have lost the functional and genotypic heterogeneity of patient tumours as well as the tumour–stroma interactions that support tumour growth. These effects are further complicated by the small quantity of live tissue obtained from patients owing to, for example, small core biopsies.…”

Section: New Methods For Tumour Manipulationmentioning

confidence: 99%

Precision medicine for cancer with next-generation functional diagnostics

et al. 2015

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Precision medicine is about matching the right drugs to the right patients. Although this approach is technology agnostic, in cancer there is a tendency to make precision medicine synonymous with genomics. However, genome-based cancer therapeutic matching is limited by incomplete biological understanding of the relationship between phenotype and cancer genotype. This limitation can be addressed by functional testing of live patient tumour cells exposed to potential therapies. Recently, several ‘next-generation’ functional diagnostic technologies have been reported, including novel methods for tumour manipulation, molecularly precise assays of tumour responses and device-based in situ approaches; these address the limitations of the older generation of chemosensitivity tests. The promise of these new technologies suggests a future diagnostic strategy that integrates functional testing with next-generation sequencing and immunoprofiling to precisely match combination therapies to individual cancer patients.

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“…Early attempts to predict in vivo response made use of immortalized cell lines in vitro . However, immortalized cell lines are highly selected subpopulations and do not adequately reflect the heterogeneous function and behavior of tumors (Cree, Glaysher, & Harvey, 2010; Dairkee et al, 2004). Consequently, there is increased interest in using primary cells in personalized in vitro models for evaluating drug response (Gerlinger, et al, 2012; Liotta & Petricoin, 2000; Longo, 2012).…”

Section: The Nature Of Patient Derived Samples: Heterogeneity Sammentioning

confidence: 99%

Personalized in vitro cancer models to predict therapeutic response: Challenges and a framework for improvement

Morgan

Johnson

Livingston

et al. 2016

Pharmacology & Therapeutics

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Personalized cancer therapy focuses on characterizing the relevant phenotypes of the patient, as well as the patient’s tumor, to predict the most effective cancer therapy. Historically, these methods have not proven predictive in regards to predicting therapeutic response. Emerging culture platforms are designed to better recapitulate the in vivo environment, thus, there is renewed interest in integrating patient samples into in vitro cancer models to assess therapeutic response. Successful examples of translating in vitro response to clinical relevance are limited due to issues with patient sample acquisition, variability and culture. We will review traditional and emerging in vitro models for personalized medicine, focusing on the technologies, microenvironmental components, and readouts utilized. We will then offer our perspective on how to apply a framework derived from toxicology and ecology towards designing improved personalized in vitro models of cancer. The framework serves as a tool for identifying optimal readouts and culture conditions, thus maximizing the information gained from each patient sample.

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A molecular 'signature' of primary breast cancer cultures; patterns resembling tumor tissue

Abstract: Background: To identify the spectrum of malignant attributes maintained outside the host environment, we have compared global gene expression in primary breast tumors and matched short-term epithelial cultures.

Cited by 55 publications

References 22 publications

Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma

Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma

Precision medicine for cancer with next-generation functional diagnostics

Personalized in vitro cancer models to predict therapeutic response: Challenges and a framework for improvement

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