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Current State of Animal (Mouse) Modeling in Melanoma Research.

Kuzu OF, Nguyen FD, Noory MA, Sharma A - Cancer Growth Metastasis (2015)

Bottom Line: Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma.Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies.As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.

ABSTRACT
Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.

No MeSH data available.


Related in: MedlinePlus

Schematic showing potential use of PDTX models in personalized therapy of melanoma. Tumors surgically removed from patients (1) are profiled in multiple platforms (2a) and also transplanted into mice for development of PDTX model (2b). PDTX model is serially propagated to test various therapeutics or their combinations (3). Based on the response of PDTX model, best therapeutic strategy is selected for the patient (4). The tumor profiles and PDTX efficacy data would be stored in the databases (5) and could provide a useful tool for the selection of therapeutic strategy for new patients (6–8).
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Related In: Results  -  Collection


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f1-cgm-suppl.1-2015-081: Schematic showing potential use of PDTX models in personalized therapy of melanoma. Tumors surgically removed from patients (1) are profiled in multiple platforms (2a) and also transplanted into mice for development of PDTX model (2b). PDTX model is serially propagated to test various therapeutics or their combinations (3). Based on the response of PDTX model, best therapeutic strategy is selected for the patient (4). The tumor profiles and PDTX efficacy data would be stored in the databases (5) and could provide a useful tool for the selection of therapeutic strategy for new patients (6–8).

Mentions: More recently, concept of PDTX mouse clinical trial is evolving and has already started to yield positive results that are helpful in guiding clinical management of the patient’s tumor.61 For this, PDTX models established from the very same patients on trial are being treated ahead of patient therapy or concurrently, and results from the mouse trial are provided in real time. Further powered by the molecular characterization of the tumors, this highly personalized approach has the potential to revolutionize the drug development and patient care.62 A potential use of PDTX models in personalized therapy of melanoma is depicted in Figure 1.


Current State of Animal (Mouse) Modeling in Melanoma Research.

Kuzu OF, Nguyen FD, Noory MA, Sharma A - Cancer Growth Metastasis (2015)

Schematic showing potential use of PDTX models in personalized therapy of melanoma. Tumors surgically removed from patients (1) are profiled in multiple platforms (2a) and also transplanted into mice for development of PDTX model (2b). PDTX model is serially propagated to test various therapeutics or their combinations (3). Based on the response of PDTX model, best therapeutic strategy is selected for the patient (4). The tumor profiles and PDTX efficacy data would be stored in the databases (5) and could provide a useful tool for the selection of therapeutic strategy for new patients (6–8).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4597587&req=5

f1-cgm-suppl.1-2015-081: Schematic showing potential use of PDTX models in personalized therapy of melanoma. Tumors surgically removed from patients (1) are profiled in multiple platforms (2a) and also transplanted into mice for development of PDTX model (2b). PDTX model is serially propagated to test various therapeutics or their combinations (3). Based on the response of PDTX model, best therapeutic strategy is selected for the patient (4). The tumor profiles and PDTX efficacy data would be stored in the databases (5) and could provide a useful tool for the selection of therapeutic strategy for new patients (6–8).
Mentions: More recently, concept of PDTX mouse clinical trial is evolving and has already started to yield positive results that are helpful in guiding clinical management of the patient’s tumor.61 For this, PDTX models established from the very same patients on trial are being treated ahead of patient therapy or concurrently, and results from the mouse trial are provided in real time. Further powered by the molecular characterization of the tumors, this highly personalized approach has the potential to revolutionize the drug development and patient care.62 A potential use of PDTX models in personalized therapy of melanoma is depicted in Figure 1.

Bottom Line: Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma.Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies.As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, PA, USA.

ABSTRACT
Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.

No MeSH data available.


Related in: MedlinePlus