Individual xenograft as a personalized therapeutic resort for women with metastatic triple-negative breast carcinoma

Bousquet, Guilhem; Feugeas, Jean-Paul; Ferreira, I.; Vercellino, Laëtitia; Jourdan, Nathalie; Bertheau, Philippe; Bazelaire, Cédric de; Barranger, Emmanuel; Janin, Anne

doi:10.1186/bcr3615

Cited by 23 publications

(20 citation statements)

References 5 publications

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“…A paradigmatic example of the use of PDX as an “avatar” for personalized cancer treatment is reported by Bousquet et al [29]. In particular, a woman with a localized left breast ductal invasive triple-negative breast carcinoma treated with chemotherapy and radiation, in accordance with French national guidelines, elicited a disease relapse.…”

Section: Pdxs Offer a Route Toward Personalized Treatmentmentioning

confidence: 99%

Patient-derived xenografts: a relevant preclinical model for drug development

Pompili¹,

Porru²,

Caruso

et al. 2016

J Exp Clin Cancer Res

114

102

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Identifying appropriate preclinical cancer models remains a major challenge in increasing the efficiency of drug development. A potential strategy to improve patient outcomes could be selecting the ‘right’ treatment in preclinical studies performed in patient-derived xenografts (PDXs) obtained by direct implants of surgically resected tumours in mice. These models maintain morphological similarities and recapitulate molecular profiling of the original tumours, thus representing a useful tool in evaluating anticancer drug response. In this review, we will present the state-of-art use of PDXs as a reliable strategy to predict clinical findings. The main advantages and limitations will also be discussed.

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Section: Pdxs Offer a Route Toward Personalized Treatmentmentioning

confidence: 99%

Patient-derived xenografts: a relevant preclinical model for drug development

Pompili¹,

Porru²,

Caruso

et al. 2016

J Exp Clin Cancer Res

114

102

View full text Add to dashboard Cite

show abstract

“…Thus, PDX models have recently been used to evaluate personalized drug treatments. The PDX model has been used to test multiple treatments for a patient’s triple-negative metastatic breast cancer, to choose the most effective drug combinations to provide better outcomes [56]. Studies have compared the response of drug treatments of PDX models from different passages and shown stable response rates across multiple passages, further supporting the phenotypic stability of these models [57, 58].…”

Section: Generation Of Pdxsmentioning

confidence: 99%

Current Update of Patient-Derived Xenograft Model for Translational Breast Cancer Research

Kawaguchi

Foster

Young

et al. 2017

J Mammary Gland Biol Neoplasia

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Despite recent advances in the treatment of patients with breast cancer (BrCa), BrCa remains the third leading cause of cancer death for women in the US due to intrinsic or acquired resistance to therapy. Continued understanding of gene expression profiling and genomic sequencing has clarified underlying intratumoral molecular heterogeneity. Recently, the patient-derived xenograft (PDX) models have emerged as a novel tool to address the issues of BrCa genomics and tumor heterogeneity, and to critically transform translational BrCa research in the preclinical setting. PDX models are generated by xenografting cancer tissue fragments obtained from patients to immune deficient mice, and can be passaged into next generations of mice. Generally, in contrast to conventional xenograft using cancer cell lines, PDXs are biologically more stable and recapitulate the individual tumor morphology, gene expression, and drug susceptibility of each patient. PDX may better model the original patient’s tumor by retaining tumor heterogeneity, gene expression, and similar response to treatment. PDX models are thus thought to be more translationally relevant, especially as a drug development tool, because PDXs can capture the genetic character and heterogeneity that exists within a single patient’s tumor and across a population of patients’ tumors. PDX models also hold enormous potential for identifying predictive markers for therapeutic response. It has been repeatedly shown that PDX models demonstrate similar levels of activity as compared to the clinical response to therapeutic interventions. Therefore, this enables identification of therapeutic interventions that can most likely benefit a patient. This allows us to address the issues of BrCa genomics and tumor heterogeneity using PDXs in “pre-clinical” trials. Herein, we reviewed recent scientific development and future perspectives using PDX models in BrCa.

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“…In fact, these authors demonstrated in PDXs derived from patients eliciting resistance to anti-EGFR inhibitors, that a dual blockade of EGFR and MEK with Cetuximab/Pimasertib combination induced a complete response in mice, thus tumours remained undetectable for more than six months. In this context, Bousquet et al, 19 showed that PDXs from a patient with an invasive triple-negative breast carcinoma which elicited a disease relapse after chemotherapy and radiation, were sensitive to Paclitaxel plus Cetuximab therapy. Following these results in PDXs, the patient was treated with Paclitaxel plus Cetuximab as second-line treatment and after 3 months almost a complete metabolic response was observed associated with a time to progression longer than previous lines of treatment.…”

Section: Patient Derived Xenograftsmentioning

confidence: 99%

The role of mouse models in translational cancer research: present and future directions

Porru

Leonetti

2017

Transl Med Rep

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A major issue in the research for new anticancer therapeutics is represented by the low number of new compounds approved for clinical use in comparison to the good success rate reported in preclinical studies. This high attrition rate could be attributed to many factors including the unsatisfactory predictive value of experiments performed in animals. To this purpose, general opinions suggest that classical models as murine tumors and xenografts do not mimic the complexity of human cancer diseases and that the use and integration of different relevant mouse models could improve the efficiency of the drug development process. In this review, we overview the present state of research in the field of mouse models for cancer and describe the advantages and limitations of the different models. Finally, strategies for improving the predictive value of animal experiments will be also discussed.

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Individual xenograft as a personalized therapeutic resort for women with metastatic triple-negative breast carcinoma

Cited by 23 publications

References 5 publications

Patient-derived xenografts: a relevant preclinical model for drug development

Patient-derived xenografts: a relevant preclinical model for drug development

Current Update of Patient-Derived Xenograft Model for Translational Breast Cancer Research

The role of mouse models in translational cancer research: present and future directions

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