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Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

ABSTRACT: Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

SUBMITTER: Pool M

PROVIDER: S-EPMC5479290 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

Pool Martin M de Boer H Rudolf HR Hooge Marjolijn N Lub-de MNL van Vugt Marcel A T M MATM de Vries Elisabeth G E EGE

Theranostics 20170527 7

Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular im ...[more]

PMID: 28638489

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Project description:'See what you treat and treat what you see, at a molecular level', could be the motto of theranostics. The concept implies diagnosis (imaging) and treatment of cells (usually cancer) using the same molecule, thus guaranteeing a targeted cytotoxic approach of the imaged tumor cells while sparing healthy tissues. As the brilliant late Sam Gambhir would say, the imaging agent acts like a 'molecular spy' and reveals where the tumoral cells are located and the extent of disease burden (diagnosis). For treatment, the same 'molecular spy' docks to the same tumor cells, this time delivering cytotoxic doses of radiation (treatment). This duality represents the concept of a 'theranostic pair', which follows the scope and fundamental principles of targeted precision and personalized medicine. Although the term theranostic was noted in medical literature in the early 2000s, the principle is not at all new to nuclear medicine. The first example of theranostic dates back to 1941 when Dr. Saul Hertz first applied radioiodine for radionuclide treatment of thyroid cells in patients with hyperthyroidism. Ever since, theranostics has been an integral element of nuclear medicine and molecular imaging. The more we understand tumor biology and molecular pathology of carcinogenesis, including specific mutations and receptor expression profiles, the more specific these 'molecular spies' can be developed for diagnostic molecular imaging and subsequent radionuclide targeted therapy (radiotheranostics). The appropriate selection of the diagnostic and therapeutic radionuclide for the 'theranostic pair' is critical and takes into account not only the type of cytotoxic radiation emission, but also the linear energy transfer (LET), and the physical half-lives. Advances in radiochemistry and radiopharmacy with new radiolabeling techniques and chelators are revolutionizing the field. The landscape of cytotoxic systemic radionuclide treatments has dramatically expanded through the past decades thanks to all these advancements. This article discusses present and promising future theranostic applications for various types of diseases such as thyroid disorders, neuroendocrine tumors (NET), pediatric malignancies, and prostate cancer (PC), and provides an outlook for future perspectives.

Project description:In today's globalized and flat world, a patient can access and seek multiple health and disease management options. A digitally enabled participatory framework that allows an evidence-based informed choice is likely to assume an immense importance in the future. In India, traditional knowledge systems, like Ayurveda, coexist with modern medicine. However, due to limited crosstalk between the clinicians of both disciplines, a patient attempts integrative medicine by seeking both options independently with limited understanding and evidence. There is a need for an integrative medicine platform with a formalized approach, which allows practitioners from the two diverse systems to crosstalk, coexist, and coevolve for an informed cross-referral that benefits the patients. To be successful, this needs frameworks that enable the bridging of disciplines through a common interface with shared ontologies. Ayurgenomics is an emerging discipline that explores the principles and practices of Ayurveda combined with genomics approaches for mainstream integration. The present review highlights how in conjunction with different disciplines and technologies this has provided frameworks for (1) the discovery of molecular correlates to build ontological links between the two systems, (2) the discovery of biomarkers and targets for early actionable interventions, (3) understanding molecular mechanisms of drug action from its usage perspective in Ayurveda with applications in repurposing, (4) understanding the network and P4 medicine perspective of Ayurveda through a common organizing principle, (5) non-invasive stratification of healthy and diseased individuals using a compendium of system-level phenotypes, and (6) developing evidence-based solutions for practice in integrative medicine settings. The concordance between the two contrasting streams has been built through extensive explorations and iterations of the concepts of Ayurveda and genomic observations using state-of-the-art technologies, computational approaches, and model system studies. These highlight the enormous potential of a trans-disciplinary approach in evolving solutions for personalized interventions in integrative medicine settings.

Dataset Information

Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

Publications

Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

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