Human tumor xenografts as model for drug testing

Mattern, J; Bak, M.; Hahn, Eric; Volm, M

doi:10.1007/bf00047755

Cited by 81 publications

(40 citation statements)

References 83 publications

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“…84 Many studies have indicated that there is a correlation between xenograft chemosensitivity and the sensitivity of the parental patient's tumor. 85 This has been reported for many clinically active drugs. Most authors who have investigated hormonal pretreatment and effectiveness of cytotoxic therapy have simultaneously treated the tumors with GC and anticancer drugs (Table 5).…”

Section: Effect Of Hormonal Pretreatment On the Effectiveness Of Cytomentioning

confidence: 65%

“…From these studies it seems that cortisone depending on the dose, has a general inhibitory action that is slight and temporary on transplantable tumors of the lymphoid series and no action on transplantable tumors of an epithelial origin. The action of cortisone on the 110 +additive-adrenal-steroidmetastases in lung, liver, treated (85) heart, brain and spleen…”

Section: Effect Of Hormonal Therapy On the Spreading Of Metastasesmentioning

confidence: 99%

See 1 more Smart Citation

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Mattern¹,

Büchler²,

Herr³

2007

Cancer Biology & Therapy

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ABBrevIAtIons DEX ABstrActGlucocorticoids have been widely used as cotreatment for patients with cancer due to potent pro-apoptotic properties in lymphoid cells, reduction of nausea and diminishing acute toxicity on normal tissue. There are now data from preclinical and, to some extent, clinical studies, demonstrating that these medicaments are highly suspicious to induce therapy resistance in the majority of malignant solid tumors-irrespective of tumor origin and the nature of specific anticancer drugs or irradiation used for treatment. Despite these huge amounts of data, the underlying mechanisms of cell type-specific signaling by these steroid hormones are just beginning to be described. This review summarizes our present understanding of a relationship between glucocorticoid-induced reversible cell cycle arrest and therapy resistance in solid tumors. We give a summary of our current knowledge of decreased proliferation rates in response to glucocorticoid pre and combination treatment which are suspicious to be involved not only in protection of normal tissues, but also in protection of solid tumors from cytotoxic effects of anticancer agents. The inhibition of cell cycle progression by pretreatment with GCs may be crucially involved in switching the balance of several interacting pathways to survival upon treatment with GCs.

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Section: Effect Of Hormonal Pretreatment On the Effectiveness Of Cytomentioning

confidence: 65%

Section: Effect Of Hormonal Therapy On the Spreading Of Metastasesmentioning

confidence: 99%

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Mattern¹,

Büchler²,

Herr³

2007

Cancer Biology & Therapy

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“…Patient-derived xenograft (PDX) models are an improvement because they more accurately model the complexity of patient tumor biology (69,70). Limitations of this approach are that each PDX model represents the tumor biology of a single patient, not all biopsies can be engrafted, the host immune system is compromised, and the tumors loose heterogeneity upon engraftment (55,71,72). Genetically engineered mouse models and other syngeneic models are necessary to evaluate a therapy in a system with an intact immune system, but these models rely on murine physiology and form tumors stochastically.…”

Section: Methods Of Detecting Mechanisms Of Response and Resistancementioning

confidence: 99%

Durability of Kinase-Directed Therapies—A Network Perspective on Response and Resistance

Murray

Miller

2015

Molecular Cancer Therapeutics

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Protein kinase-directed cancer therapies yield impressive initial clinical responses, but the benefits are typically transient. Enhancing the durability of clinical response is dependent upon patient selection, using drugs with more effective pharmacology, anticipating mechanisms of drug resistance, and applying concerted drug combinations. Achieving these tenets requires an understanding of the targeted kinase's role in signaling networks, how the network responds to drug perturbation, and patient-topatient network variations. Protein kinases create sophisticated, malleable signaling networks with fidelity coded into the processes that regulate their presence and function. Robust and reliable signaling is facilitated through network processes (e.g., feedback regulation, and compensatory signaling). The routine use of kinase-directed therapies and advancements in both genomic analysis and tumor cell biology are illuminating the complexity of tumor network biology and its capacity to respond to perturbations. Drug efficacy is attenuated by alterations of the drug target (e.g., steric interference, compensatory activity, and conformational changes), compensatory signaling (bypass mechanisms and phenotype switching), and engagement of other oncogenic capabilities (polygenic disease). Factors influencing anticancer drug response and resistance are examined to define the behavior of kinases in network signaling, mechanisms of drug resistance, drug combinations necessary for durable clinical responses, and strategies to identify mechanisms of drug resistance.

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“…42 Currently, subcutaneous PDX models, wherein tumor cells are transplanted underneath the skin of the hindquarters or in the mammary fat pad dominate the field of primary xenografts, succeeding intra-ocular, embryonic, and athymic systems. 29,61 Many groups also transplant cells under the kidney capsule or orthotopically; the latter of which may better replicate the tumor microenvironment than subcutaneous models, and thus may be most physiologically relevant. Regardless of the transplantation site, the cellular complexity and architecture of PDX tumor models remains remarkably faithful to the tumor in its natural state in most cases-complete with invading vasculature and supporting stromal cells (Figure 1d).…”

Section: Pdxs: Models For the 21st Centurymentioning

confidence: 99%

“…For example, breast cancer PDX models appear to be particularly difficult to establish, with a 27% engraftment rate in the most successful laboratories, compared with ovarian (65%), lung (50%), melanoma (59%), and colorectal (68%) cancer. 51,61 Mounting evidence suggests that the exact mouse strain (eg, NOD/SCID vs NSG) does not significantly impact engraftment efficiency of most solid tumor types, but strain differences can impact the rate at which tumors arise. 29,64,65 PDX tumor models can be propagated as either discrete tumor fragments or as single-cell suspensions.…”

Section: Pdxs: Models For the 21st Centurymentioning

confidence: 99%

Patient-derived xenografts, the cancer stem cell paradigm, and cancer pathobiology in the 21st century

Williams

Anderson

Santaguida

et al. 2013

Laboratory Investigation

168

166

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Cancer is a heterogeneous disease manifest in many forms. Tumor histopathology can differ significantly among patients and cellular heterogeneity within tumors is common. A primary goal of cancer biologists is to better understand tumorigenesis and cancer progression; however, the complex nature of tumors has posed a substantial challenge to unlocking cancer's secrets. The cancer stem cell (CSC) paradigm for the pathobiology of solid tumors appropriately acknowledges phenotypic and functional tumor cell heterogeneity observed in solid tumors and accounts for the disconnect between drug approval based on response and the general inability of approved therapies to meaningfully impact survival due to their failure to eradicate these most important of cellular targets. First proposed to exist decades ago, CSC have only recently begun to be precisely identified due to technical advancements that facilitate identification, isolation, and interrogation of distinct tumor cell subpopulations with differing ability to form and perpetuate tumors. Precise identification of CSC populations and the complete hierarchy of cells within solid tumors will facilitate more accurate characterization of patient subtypes and ultimately contribute to more personalized and effective therapies. Rapid advancement in the understanding of tumor biology as it exists in patients requires cooperation among institutions, surgeons, pathologists, cancer biologists and patients alike, primarily because this translational research is best done with patient-derived tissue grown in the xenograft setting as patient-derived xenografts. This review calls for a broader change in the approaches taken to study cancer pathobiology, highlights what implications the CSC paradigm has for pathologists and cancer biologists alike, and calls for greater collaboration between institutions, physicians and scientists in order to more rapidly advance our collective understanding of cancer.

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Human tumor xenografts as model for drug testing

Cited by 81 publications

References 83 publications

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Durability of Kinase-Directed Therapies—A Network Perspective on Response and Resistance

Patient-derived xenografts, the cancer stem cell paradigm, and cancer pathobiology in the 21st century

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