Can Systems Biology Advance Clinical Precision Oncology?

Rocca, Andrea; Kholodenko, Boris N.

doi:10.3390/cancers13246312

Cited by 12 publications

(11 citation statements)

References 215 publications

(243 reference statements)

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“…Before its psychiatric application, personalized medicine had brought significant diagnostic and therapeutical advances in oncology where the identification of the molecular target of the drug, the mechanisms of resistance to targeted compounds, and the best pharmacological combinations for a specific tumor promoted the optimal individual treatment selection [ 3 ].…”

Section: The Limitations Of Personalized Medicine In Psychiatrymentioning

confidence: 99%

Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry

Alciati

Reggiani

Caldirola

et al. 2022

JPM

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The polygenic and multifactorial nature of many psychiatric disorders has hampered implementation of the personalized medicine approach in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into iPSCs to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. In this regard, iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that emulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and to conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depressive disorder, bipolar disorder, and autism spectrum disorder. Future perspectives will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions so as to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways by which to build a disease model that considers individual variability and tailors personalized treatments.

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Section: The Limitations Of Personalized Medicine In Psychiatrymentioning

confidence: 99%

Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry

Alciati

Reggiani

Caldirola

et al. 2022

JPM

View full text Add to dashboard Cite

show abstract

“…Mathematical models find associations in data sets and allow for data modeling using a variety of biomarkers and patient characteristics. These models can be used to select chemotherapy agents based on computational models of apoptotic pathways and to identify personalized combination treatments based on tumor biopsy data ( 80 ). Models must first be trained on existing data and validated with untrained data before they can predict outcomes for existing data sets ( 81 ).…”

Section: Beyond the Benchtop: Mathematical Models And Artificial Inte...mentioning

confidence: 99%

Functional Drug Screening in the Era of Precision Medicine

2022

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The focus of precision medicine is providing the right treatment to each unique patient. This scientific movement has incited monumental advances in oncology including the approval of effective, targeted agnostic therapies. Yet, precision oncology has focused largely on genomics in the treatment decision making process, and several recent clinical trials demonstrate that genomics is not the only variable to be considered. Drug screening in three dimensional (3D) models, including patient derived organoids, organs on a chip, xenografts, and 3D-bioprinted models provide a functional medicine perspective and necessary complement to genomic testing. In this review, we discuss the practicality of various 3D drug screening models and each model’s ability to capture the patient’s tumor microenvironment. We highlight the potential for enhancing precision medicine that personalized functional drug testing holds in combination with genomic testing and emerging mathematical models.

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“…Before its psychiatric application, personalized medicine has brought significant diagnostic and therapeutical advances in oncology where the identification of the molecular target of the drug, the mechanisms of resistance to targeted compounds, the best pharmacological combinations for a specific tumor, promoted the optimal individual treatment selection [3].…”

Section: The Limitations Of Personalized Medicine In Psychiatrymentioning

confidence: 99%

Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry

Alciati¹,

Reggiani²,

Caldirola³

et al. 2022

Preprint

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The polygenic and multifactorial nature of many psychiatric disorders has hampered the personalized medicine approach implementation in clinical practice. However, induced pluripotent stem cell (iPSC) technology has emerged as an innovative tool for patient-specific disease modeling to expand the pathophysiology knowledge and treatment perspectives in the last decade. Current technologies enable adult human somatic cell reprogramming into induced pluripotent stem cells (iPSCs) to generate neural cells and direct neural cell conversion to model organisms that exhibit phenotypes close to human diseases, thereby effectively representing relevant aspects of neuropsychiatric disorders. iPSCs reflect patient pathophysiology and pharmacological responsiveness, particularly when cultured under conditions that recapitulate spatial tissue organization in brain organoids. Recently, the application of iPSCs has been frequently associated with gene editing that targets the disease-causing gene to deepen the illness pathophysiology and conduct drug screening. Moreover, gene editing has provided a unique opportunity to repair the putative causative genetic lesions in patient-derived cells. Here, we review the use of iPSC technology to model and potentially treat neuropsychiatric disorders by illustrating the key studies on a series of mental disorders, including schizophrenia, major depression disorder, bipolar disorder, and autism spectrum disorder. The future perspective will involve the development of organ-on-a-chip platforms that control the microenvironmental conditions to reflect individual pathophysiological by adjusting physiochemical parameters according to personal health data. This strategy could open new ways to build a disease model that considers individual variability and tailors personalized treatments.

show abstract

Can Systems Biology Advance Clinical Precision Oncology?

Cited by 12 publications

References 215 publications

Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry

Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry

Functional Drug Screening in the Era of Precision Medicine

Human-Induced Pluripotent Stem Cell Technology: Toward the Future of Personalized Psychiatry

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