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Ways to improve tumor uptake and penetration of drugs into solid tumors

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193509 Year: Pages: 129 DOI: 10.3389/978-2-88919-350-9 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General) --- Therapeutics --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Abstract

The main scope of this topic is to give an update on pharmacologic and non-pharmacologic approaches to enhance uptake and penetration of cancer drugs into tumors. Inadequate accumulation of drugs in tumors has emerged over the last decade as one of the main problems underlying therapeutic failure and drug resistance in the treatment of cancer. Insufficient drug uptake and penetration is causally related to the abnormal tumor architecture. Thus, poor vascularization, increased resistance to blood flow and impaired blood supply represent a first obstacle to the delivery of antitumor drugs to tumor tissue. Decreased or even inverted transvascular pressure gradients compromise convective delivery of drugs. Eventually, an abnormal extracellular matrix offers increased frictional resistance to tumor drug penetration. Abnormal tumor architecture also changes the biology of tumor cells, which contributes to drug resistance through several different mechanisms. The variability in vessel location and structure can make many areas of the tumor hypoxic, which causes the tumor cells to become quiescent and thereby resistant to many antitumor drugs. In addition, the abnormally long distance of part of the tumor cell population from blood vessels provides a challenge to delivering cancer drugs to these cells. We have recently proposed additional mechanisms of tumor drug resistance, which are also related to abnormal tumor architecture. First, increased interstitial fluid pressure can by itself induce drug resistance through the induction of resistance-promoting paracrine factors. Second, the interaction of drug molecules with vessel- proximal tumor cell layers may also induce the release of these factors, which can spread throughout the cancer, and induce drug resistance in tumor cells distant from blood vessels. As can be seen, abnormal tumor architecture, inadequate drug accumulation and tumor drug resistance are tightly linked phenomena, suggesting the need to normalize the tumor architecture, including blood vessels, and/or increase the accumulation of cancer drugs in tumors in order to increase therapeutic effects. Indeed, several classes of drugs (that we refer to as promoter drugs) have been described, that promote tumor uptake and penetration of antitumor drugs, including those that are vasoactive, modify the barrier function of tumor vessels, debulk tumor cells, and overcome intercellular and stromal barriers. In addition, also non-pharmacologic approaches have been described that enhance tumor accumulation of effector drugs (e.g. convection-enhanced delivery, hyperthermia, etc.). Some drugs that have already received regulatory approval (e.g. the anti-VEGF antibody bevacizumab) exert antitumor effects at least in part through normalization of the tumor vasculature and enhancement of the accumulation of effector drugs. Other drugs, acting through different mechanisms of action, are now in clinical development (e.g. NGR-TNF in phase II/III studies) and others are about to enter clinical investigation (e.g. JO-1).

Renal Cell Carcinoma

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ISBN: 9783039286386 / 9783039286393 Year: Pages: 500 DOI: 10.3390/books978-3-03928-639-3 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2020-06-09 16:38:57
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Abstract

Renal cancer is a health problem of major concern worldwide. Although tyrosine kinase inhibitors and immune check-point blockade treatments, alone or in combination, are giving promising results, failures are quite frequent due to intratumor heterogeneity and to the acquisition of drug resistance. The spectrum of renal cell carcinoma subtypes is wide. Up to 70–80% of renal tumors are clear cell renal cell carcinomas, a clinically aggressive tumor subtype linked to VHL gene inactivation. Next in frequency, the papillary renal cell carcinoma category encompasses an intricate puzzle of classic and newly described entities with poorly defined limits, some of them pending definite clarification. Likewise, the chromophobe–oncocytoma duality, the so-called hybrid tumors and oncocytic neoplasms, remain to be well profiled. Finally, a growing list of very uncommon renal tumors linked to specific molecular signatures fulfill the current portrait of renal cell neoplasia. This Special Issue of Cancers regards RCC from very different perspectives, from the intimate basic mechanisms governing this disease to the clinical practice principles of their diagnoses and treatments. The interested reader will have the opportunity to contact with some of the most recent findings and will be updated with excellent reviews.

Keywords

ghrelin --- aurora A --- MMP10 --- invasion --- sarcomatoid --- RCC --- immunotherapy --- checkpoint inhibitors --- survival --- PD-L1 --- chronic kidney disease --- nephrectomy --- overall survival --- recurrence free survival --- renal cell carcinoma --- statins --- uric acid --- intratumour heterogeneity --- metastatic ccRCC --- copy number alteration --- mutation --- gene expression --- MiT family translocation renal cell carcinoma --- Xp11 translocation renal cell carcinoma --- t(6 --- 11) translocation renal cell carcinoma --- FISH --- TFE3 --- TFEB --- TFEB-amplified renal cell carcinoma --- renal cell carcinoma --- immune checkpoint inhibitors --- tyrosine kinase inhibitors --- efficacy --- toxicity --- cytoreductive nephrectomy --- Papillary renal cell carcinoma (pRCC) --- proteome profiling --- metabolome profiling --- glutathione metabolism --- metabolic reprogramming --- IL4R? --- IL13R?1 --- renal cell carcinoma --- JAK2 --- FOXO3 --- clear cell renal cell carcinoma --- identification of circular RNAs --- experimental validation of circular RNA --- diagnostic and prognostic markers --- circular RNAs in a clinico-genomic predictive model --- cancer-specific survival --- recurrence-free survival --- overall survival --- chromophobe renal cell carcinoma --- pale cell --- eosinophilic variant --- chromosomal loss --- copy number analysis --- renal cell carcinoma --- clear cell renal cell carcinoma --- AMP-activated protein kinases --- immunohistochemistry --- prognosis --- SMAD proteins --- transforming growth factor beta --- renal cell cancer --- microRNA --- metabolome --- proliferation --- PPP --- pentose phosphate pathway --- TCA cycle --- miR-155-5p --- miR-146a-5p --- TCGA --- renal cell carcinoma --- metastasis --- MTA2 --- MMP-9 --- miR-133b --- kidney cancer --- immunotherapy --- renal cell --- inflammation markers --- programmed death-ligand 1 --- immune checkpoint inhibitors --- prognostic factors --- predictive factors --- glutathione transferase omega 1 --- glutathione transferase omega 2 --- polymorphism --- PI3K/Akt/mTOR --- Raf/MEK/ERK --- IL-1? --- pro-IL-1? --- gene signature --- renal cancer --- survival prediction --- polybromo-1 --- PBRM1 --- renal cell carcinoma --- biomarker --- prognosis --- predictive role --- collecting duct carcinoma --- RNA sequencing --- solute carrier proteins --- kidney --- renal cell carcinoma --- molecular genetic features --- practical approach --- review --- renal cell carcinoma --- sarcomatoid --- immunotherapy --- renal cell carcinoma --- checkpoint inhibitors --- VEGF inhibitors --- mTOR inhibitors --- kidney --- emerging entity --- new entity --- oncocytic renal tumor --- unclassified renal cell carcinoma --- unclassified renal tumor --- anaplastic lymphoma kinase rearrangement --- ALK --- ESC --- HOT --- LOT --- drug sensitivity --- immune infiltration --- renal cancer --- targeted therapy --- tumor slice culture --- clear cell Renal Cell Carcinoma --- urine --- glycoproteomics --- N-glycomapping --- label-free --- glycomarkers --- everolimus --- EVI1 --- genetic association --- mTOR --- clear cell renal cell carcinoma --- curcumin --- renal cell cancer --- tumor adhesion --- tumor migration --- integrins --- NK cells --- kidney cancer --- renal cell carcinoma --- IL-2 --- cancer immunotherapy --- tumor microenvironment --- von Hippel–Lindau --- EMT like --- hyperosmolality --- chromophobe renal cell carcinoma --- copy number loss --- CDKN1A expression --- patient survival --- prognosis --- n/a

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