Dataset Information

A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma.

ABSTRACT:

Background

Metastasis is a hallmark of cancer and responsible for most cancer deaths. Migrastatics were defined as drugs interfering with all modes of cancer cell invasion and thus cancers' ability to metastasise. First anti-metastatic treatments have recently been approved.

Methods

We used bioinformatic analyses of publicly available melanoma databases. Experimentally, we performed in vitro target validation (including 2.5D cell morphology analysis and mass spectrometric analysis of RhoA binding partners), developed a new traceable spontaneously metastasising murine melanoma model for in vivo validation, and employed histology (haematoxylin/eosin and phospho-myosin II staining) to confirm drug action in harvested tumour tissues.

Results

Unbiased and targeted bioinformatic analyses identified the Rho kinase (ROCK)-myosin II pathway and its various components as potentially relevant targets in melanoma. In vitro validation demonstrated redundancy of several RhoGEFs upstream of RhoA and confirmed ROCK as a druggable target downstream of RhoA. The anti-metastatic effects of two ROCK inhibitors were demonstrated through in vivo melanoma metastasis tracking and inhibitor effects also confirmed ex vivo by digital pathology.

Conclusions

We proposed a migrastatic drug development pipeline. As part of the pipeline, we provide a new traceable spontaneous melanoma metastasis model for in vivo quantification of metastasis and anti-metastatic effects by non-invasive imaging.

SUBMITTER: Maiques O

PROVIDER: S-EPMC8405734 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma.

Maiques Oscar O Fanshawe Bruce B Crosas-Molist Eva E Rodriguez-Hernandez Irene I Volpe Alessia A Cantelli Gaia G Boehme Lena L Orgaz Jose L JL Mardakheh Faraz K FK Sanz-Moreno Victoria V Fruhwirth Gilbert O GO

British journal of cancer 20210625 5

<h4>Background</h4>Metastasis is a hallmark of cancer and responsible for most cancer deaths. Migrastatics were defined as drugs interfering with all modes of cancer cell invasion and thus cancers' ability to metastasise. First anti-metastatic treatments have recently been approved.<h4>Methods</h4>We used bioinformatic analyses of publicly available melanoma databases. Experimentally, we performed in vitro target validation (including 2.5D cell morphology analysis and mass spectrometric analysis ...[more]

PMID: 34172930

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Dataset Information

A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma.

Background

Methods

Results

Conclusions

Publications

A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma.

Similar Datasets

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