Understanding and targeting resistance mechanisms in cancer

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 22, 2023

Resistance to cancer therapies has been a commonly observed phenomenon in clinical practice, which is one of the major causes treatment failure and poor patient survival. The reduced responsiveness cells multifaceted that can arise from genetic, epigenetic, microenvironmental factors. Various mechanisms have discovered extensively studied, including drug inactivation, intracellular accumulation by uptake or increased efflux, target alteration, activation compensatory pathways for cell survival, regulation DNA repair death, tumor plasticity, microenvironments (TMEs). To overcome resistance, variety strategies proposed, are designed enhance effectiveness reduce resistance. These include identifying biomarkers predict response new targets, developing targeted drugs, combination targeting multiple signaling pathways, modulating TME. present article focuses on different resistance corresponding tackling approaches with recent updates. Perspectives polytherapy mechanisms, novel nanoparticle delivery systems, advanced design tools overcoming also reviewed.

Язык: Английский

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Programming 3D curved mesosurfaces using microlattice designs

Science, Год журнала: 2023, Номер 379(6638), С. 1225 - 1232

Опубликована: Март 23, 2023

Cellular microstructures form naturally in many living organisms (e.g., flowers and leaves) to provide vital functions synthesis, transport of nutrients, regulation growth. Although heterogeneous cellular are believed play pivotal roles their three-dimensional (3D) shape formation, programming 3D curved mesosurfaces with designs remains elusive man-made systems. We report a rational microlattice design that allows transformation 2D films into programmable through mechanically guided assembly. Analytical modeling machine learning-based computational approach serve as the basis for determine patterns required target surfaces. About 30 geometries presented, including both regular biological mesosurfaces. Demonstrations include conformable cardiac electronic device, stingray-like dual mode actuator, cell scaffold.

Язык: Английский

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Organoids: The current status and biomedical applications

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 17, 2023

Organoids are three-dimensional (3D) miniaturized versions of organs or tissues that derived from cells with stem potential and can self-organize differentiate into 3D cell masses, recapitulating the morphology functions their in vivo counterparts. Organoid culture is an emerging technology, organoids various tissues, such as brain, lung, heart, liver, kidney, have been generated. Compared traditional bidimensional culture, organoid systems unique advantage conserving parental gene expression mutation characteristics, well long-term maintenance function biological characteristics vitro. All these features open up new opportunities for drug discovery, large-scale screening, precision medicine. Another major application disease modeling, especially hereditary diseases difficult to model vitro modeled by combining genome editing technologies. Herein, we introduce development current advances technology field. We focus on applications basic biology clinical research, also highlight limitations future perspectives. hope this review provide a valuable reference developments organoids.

Язык: Английский

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3D bioprinted cancer models: from basic biology to drug development

Nature reviews. Cancer, Год журнала: 2022, Номер 22(12), С. 679 - 692

Опубликована: Окт. 24, 2022

Язык: Английский

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Chemiluminescent probes in cancer biology

Nature Reviews Bioengineering, Год журнала: 2023, Номер 1(9), С. 648 - 664

Опубликована: Июнь 19, 2023

Язык: Английский

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Organ‐On‐A‐Chip Models of the Blood–Brain Barrier: Recent Advances and Future Prospects

Small, Год журнала: 2022, Номер 18(39)

Опубликована: Авг. 17, 2022

The human brain and central nervous system (CNS) present unique challenges in drug development for neurological diseases. One major obstacle is the blood-brain barrier (BBB), which hampers effective delivery of therapeutic molecules into while protecting it from blood-born neurotoxic substances maintaining CNS homeostasis. For BBB research, traditional vitro models rely upon Petri dishes or Transwell systems. However, these static lack essential microenvironmental factors such as shear stress proper cell-cell interactions. To this end, organ-on-a-chip (OoC) technology has emerged a new modeling approach to better recapitulate highly dynamic vivo microenvironment so-called neural vascular unit (NVU). Such BBB-on-a-chip have made substantial progress over last decade, concurrently there been increasing interest various diseases Alzheimer's disease Parkinson's using OoC technology. In addition, with recent advances other scientific technologies, several opportunities improve platform via multidisciplinary approaches are available. review, an overview NVU provided, applications personalized medicine discovery discussed, current future directions delineated.

Язык: Английский

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Immunotherapy of glioblastoma explants induces interferon-γ responses and spatial immune cell rearrangements in tumor center, but not periphery

Science Advances, Год журнала: 2022, Номер 8(26)

Опубликована: Июль 1, 2022

A patient-tailored, ex vivo drug response platform for glioblastoma (GBM) would facilitate therapy planning, provide insights into treatment-induced mechanisms in the immune tumor microenvironment (iTME), and enable discovery of biomarkers response. We cultured regionally annotated GBM explants perfusion bioreactors to assess iTME responses immunotherapy. Explants were treated with anti-CD47, anti–PD-1, or their combination, analyzed by multiplexed microscopy [CO-Detection indEXing (CODEX)], enabling spatially resolved identification >850,000 single cells, accompanied explant secretome interrogation. Center periphery differed cell type soluble factor composition, subset displayed increased interferon-γ levels, which correlated shifts composition within specified tissue compartments. Our study demonstrates that immunotherapy enables an active antitumoral center provides a framework multidimensional personalized assessment

Язык: Английский

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Glioblastoma-on-a-chip construction and therapeutic applications

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Июль 12, 2023

Glioblastoma (GBM) is the most malignant type of primary intracranial tumor with a median overall survival only 14 months, very poor prognosis and recurrence rate 90%. It difficult to reflect complex structure function GBM microenvironment in vivo using traditional vitro models. GBM-on-a-chip platforms can integrate biological or chemical functional units into chip, mimicking functions cells. This technology has shown great potential for applications personalized precision medicine immunotherapy. In recent years, there have been efforts construct models based on microfluidics bioprinting. A number research teams begun use investigation progression mechanisms, drug candidates, therapeutic approaches. review first briefly discusses bioprinting technologies construction. Second, we classify non-surgical treatments pre-clinical three categories (chemotherapy, immunotherapy other therapies) focus each category. Last, demonstrate that organ-on-a-chip field still its initial stage provide future perspectives directions field.

Язык: Английский

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Embedded Bioprinting of Breast Tumor Cells and Organoids Using Low‐Concentration Collagen‐Based Bioinks

Advanced Healthcare Materials, Год журнала: 2023, Номер 12(26)

Опубликована: Июль 9, 2023

Bioinks for 3D bioprinting of tumor models should not only meet printability requirements but also accurately maintain and support phenotypes surrounding cells to recapitulate key hallmarks. Collagen is a major extracellular matrix protein solid tumors, low viscosity collagen solution has made bioprinted cancer challenging. This work produces embedded, breast organoid using low-concentration I based bioinks. The biocompatible physically crosslinked silk fibroin hydrogel used generate the bath embedded printing. composition bioink optimized with thermoresponsive hyaluronic acid-based polymer both noninvasive epithelial invasive cells, as well cancer-associated fibroblasts. Mouse organoids are mimic in vivo morphology. A vascularized model created similar strategy, significantly enhanced vasculature formation under hypoxia. study shows great potential utilizing collagen-based advancing understanding cell biology facilitating drug discovery research.

Язык: Английский

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Harnessing 3D in vitro systems to model immune responses to solid tumours: a step towards improving and creating personalized immunotherapies

Nature reviews. Immunology, Год журнала: 2023, Номер 24(1), С. 18 - 32

Опубликована: Июль 4, 2023

Язык: Английский

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