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Cancer models in preclinical research:A chronicle review of advancement in effective cancer research

Animal Models and Experimental Medicine 2021年第2期4卷 87-103页

作者： Humna Sajjad Saiqa Imtiaz tayyaba Noor Yusra hasan Siddiqui Anila Sajjad Muhammad Zia Department of Biotechnology Quaid-i-Azam UniversityIslamabadPakistan

Cancer is a major stress for public well-being and is the most dreadful disease.The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies.Cancer models are either naturally existing or artificially prepared experimental systems that show similar features with human tumors though the heterogeneous nature of the tumor is very familiar.The choice of the most fitting model to best reflect the given tumor system is one of the real difficulties for cancer examination.Therefore,vast studies have been conducted on the cancer models for developing a better understanding of cancer invasion,progression,and early detection.These models give an insight into cancer etiology,molecular basis,host tumor interaction,the role of microenvironment,and tumor heterogeneity in tumor metastasis.These models are also used to predict novel can-cer markers,targeted therapies,and are extremely helpful in drug development.In this review,the potential of cancer models to be used as a platform for drug screening and therapeutic discoveries are highlighted.Although none of the cancer models is regarded as ideal because each is associated with essential caveats that restraint its application yet by bridging the gap between preliminary cancer research and transla-tional medicine.However,they promise a brighter future for cancer treatment.

关键词： cancer cell lines computational cancer models genetically engineered mouse models organoids patient-derived xenografts personalized medicine

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Is tumor cell specificity distinct from tumor selectivity in vivo?A quantitative NIR molecular imaging analysis of nanoliposome targeting

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Nano Research 2021年第5期14卷 1344-1354页

作者： Girgis Obaid Kimberley Samkoe Kenneth Tichauer Shazia Bano Yeonjae Park Zachary Silber Sassan Hodge Susan Callaghan Mina Guirguis Srivalleesha Mallidi Brian Pogue Tayyaba Hasan Wellman Center for Photomedicine Massachusetts General Hospital and Harvard Medical SchoolBostonMA02114USA Department of Bioengineering University of Texas at DallasRichardsonTX75080USA Thayer School of Engineering Dartmouth CollegeHanoverNH037551USA Armour College of Engineering Illinois Institute of TechnologyChicagoIL60616USA Division of Health Sciences and Technology Harvard University and Massachusetts Institute of TechnologyCambridgeMA02139USA

The significance and ability for receptor targeted nanoliposomes(tNLs)to bind to their molecular targets in solid tumors in vivo has been questioned,particularly as the efficiency of their tumor accumulation and selectivity is not always predictive of their efficacy or molecular specificity.This study presents,for the first time,in situ near-infrared(NIR)molecular imaging-based quantitation of the in vivo specificity of tNLs for their target receptors,as opposed to tumor selectivity,which includes influences of enhanced tumor permeability and retention.Results show that neither tumor delivery nor selectivity(tumor-to-normal ratio)of cetuximab and IRDye conjugated tNLs correlate with epidermal growth factor receptor(EGFR)expression in U251,U87,and 9L tumors,and in fact underrepresent their imaging-derived molecular specificity by up to 94.2%.Conversely,their in vivo specificity,which we quantify as the concentration of tNL-reported tumor EGFR provided by NIR molecular imaging,correlates positively with EGFR expression levels in vitro and ex vivo(Pearson’s r=0.92 and 0.96,respectively).This study provides a unique opportunity to address the problematic disconnect between tNL synthesis and in vivo specificity.The findings encourage their continued adoption as platforms for precision medicine,and facilitates intelligent synthesis and patient customization in order to improve safety profiles and therapeutic outcomes.

关键词： molecular recognition receptors nanoparticles specificity cancer

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