Necrosis in the Tumor Microenvironment and Its Role in Cancer Recurrence

Karsch-Bluman, Adi; Benny, Ofra

doi:10.1007/978-3-030-35727-6_6

Cited by 19 publications

(13 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The method’s ability to discriminate between distinct biological compartments was demonstrated by comparing the lipid profiles of viable and necrotic tumor tissue ( Table 2 and Figure 1 ). Necrotic foci appear when nutrient and oxygen deprivation causing cell death occurs and is often the result of a deteriorating microenvironment in rapidly growing tumors [ 35 ]. It has previously been shown that DESI-MSI can identify necrosis in fresh frozen tumor specimens [ 36 ] based on the presence of lipid species specific to viable and necrotic tissue, respectively.…”

Section: Discussionmentioning

confidence: 99%

Reproducible Lipid Alterations in Patient-Derived Breast Cancer Xenograft FFPE Tissue Identified with MALDI MSI for Pre-Clinical and Clinical Application

et al. 2021

View full text Add to dashboard Cite

The association between lipid metabolism and long-term outcomes is relevant for tumor diagnosis and therapy. Archival material such as formalin-fixed and paraffin embedded (FFPE) tissues is a highly valuable resource for this aim as it is linked to long-term clinical follow-up. Therefore, there is a need to develop robust methodologies able to detect lipids in FFPE material and correlate them with clinical outcomes. In this work, lipidic alterations were investigated in patient-derived xenograft of breast cancer by using a matrix-assisted laser desorption ionization mass spectrometry (MALDI MSI) based workflow that included antigen retrieval as a sample preparation step. We evaluated technical reproducibility, spatial metabolic differentiation within tissue compartments, and treatment response induced by a glutaminase inhibitor (CB-839). This protocol shows a good inter-day robustness (CV = 26 ± 12%). Several lipids could reliably distinguish necrotic and tumor regions across the technical replicates. Moreover, this protocol identified distinct alterations in the tissue lipidome of xenograft treated with glutaminase inhibitors. In conclusion, lipidic alterations in FFPE tissue of breast cancer xenograft observed in this study are a step-forward to a robust and reproducible MALDI-MSI based workflow for pre-clinical and clinical applications.

show abstract

Section: Discussionmentioning

confidence: 99%

Reproducible Lipid Alterations in Patient-Derived Breast Cancer Xenograft FFPE Tissue Identified with MALDI MSI for Pre-Clinical and Clinical Application

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This hypoxic environment at the center displays an unregulated expression of the hypoxia-inducible factor (HIF), which contributes to establishing therapeutic resistance mechanisms. Both hypoxia and necrosis play crucial roles in anticancer drug resistance mechanisms ( Karsch-Bluman et al, 2019 ; Sharma et al, 2019 ; Karsch Bluman and Benny, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Kinetics of Nanomedicine in Tumor Spheroid as an In Vitro Model System for Efficient Tumor-Targeted Drug Delivery With Insights From Mathematical Models

Roy¹,

Garg²,

Barman³

et al. 2021

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Numerous strategies have been developed to treat cancer conventionally. Most importantly, chemotherapy shows its huge promise as a better treatment modality over others. Nonetheless, the very complex behavior of the tumor microenvironment frequently impedes successful drug delivery to the tumor sites that further demands very urgent and effective distribution mechanisms of anticancer drugs specifically to the tumor sites. Hence, targeted drug delivery to tumor sites has become a major challenge to the scientific community for cancer therapy by assuring drug effects to selective tumor tissue and overcoming undesired toxic side effects to the normal tissues. The application of nanotechnology to the drug delivery system pays heed to the design of nanomedicine for specific cell distribution. Aiming to limit the use of traditional strategies, the adequacy of drug-loaded nanocarriers (i.e., nanomedicine) proves worthwhile. After systemic blood circulation, a typical nanomedicine follows three levels of disposition to tumor cells in order to exhibit efficient pharmacological effects induced by the drug candidates residing within it. As a result, nanomedicine propounds the assurance towards the improved bioavailability of anticancer drug candidates, increased dose responses, and enhanced targeted efficiency towards delivery and distribution of effective therapeutic concentration, limiting toxic concentration. These aspects emanate the proficiency of drug delivery mechanisms. Understanding the potential tumor targeting barriers and limiting conditions for nanomedicine extravasation, tumor penetration, and final accumulation of the anticancer drug to tumor mass, experiments with in vivo animal models for nanomedicine screening are a key step before it reaches clinical translation. Although the study with animals is undoubtedly valuable, it has many associated ethical issues. Moreover, individual experiments are very expensive and take a longer time to conclude. To overcome these issues, nowadays, multicellular tumor spheroids are considered a promising in vitro model system that proposes better replication of in vivo tumor properties for the future development of new therapeutics. In this review, we will discuss how tumor spheroids could be used as an in vitro model system to screen nanomedicine used in targeted drug delivery, aiming for better therapeutic benefits. In addition, the recent proliferation of mathematical modeling approaches gives profound insight into the underlying physical principles and produces quantitative predictions. The hierarchical tumor structure is already well decorous to be treated mathematically. To study targeted drug delivery, mathematical modeling of tumor architecture, its growth, and the concentration gradient of oxygen are the points of prime focus. Not only are the quantitative models circumscribed to the spheroid, but also the role of modeling for the nanoparticle is equally inevitable. Abundant mathematical models have been set in motion for more elaborative and meticulous designing of nanomedicine, addressing the question regarding the objective of nanoparticle delivery to increase the concentration and the augmentative exposure of the therapeutic drug molecule to the core. Thus, to diffuse the dichotomy among the chemistry involved, biological data, and the underlying physics, the mathematical models play an indispensable role in assisting the experimentalist with further evaluation by providing the admissible quantitative approach that can be validated. This review will provide an overview of the targeted drug delivery mechanism for spheroid, using nanomedicine as an advantageous tool.

show abstract

“…Tumor necrotic debris caused by hypoxia can release different signals leading to cancer progression [ 159 ]. Macrophages can accumulate in perivascular and perinecrotic niches in tumors [ 160 ] where they can operate as immune scavengers to sweep away cellular debris [ 161 ].…”

Section: Hypoxia-driven Crosstalk Between Tumor Cells and Tamsmentioning

confidence: 99%

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

et al. 2022

View full text Add to dashboard Cite

Given that hypoxia is a persistent physiological feature of many different solid tumors and a key driver for cancer malignancy, it is thought to be a major target in cancer treatment recently. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME), which have a large impact on tumor development and immunotherapy. TAMs massively accumulate within hypoxic tumor regions. TAMs and hypoxia represent a deadly combination because hypoxia has been suggested to induce a pro-tumorigenic macrophage phenotype. Hypoxia not only directly affects macrophage polarization, but it also has an indirect effect by altering the communication between tumor cells and macrophages. For example, hypoxia can influence the expression of chemokines and exosomes, both of which have profound impacts on the recipient cells. Recently, it has been demonstrated that the intricate interaction between cancer cells and TAMs in the hypoxic TME is relevant to poor prognosis and increased tumor malignancy. However, there are no comprehensive literature reviews on the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs. Therefore, this review has the aim to collect all recently available data on this topic and provide insights for developing novel therapeutic strategies for reducing the effects of hypoxia.

show abstract

Necrosis in the Tumor Microenvironment and Its Role in Cancer Recurrence

Cited by 19 publications

References 109 publications

Reproducible Lipid Alterations in Patient-Derived Breast Cancer Xenograft FFPE Tissue Identified with MALDI MSI for Pre-Clinical and Clinical Application

Reproducible Lipid Alterations in Patient-Derived Breast Cancer Xenograft FFPE Tissue Identified with MALDI MSI for Pre-Clinical and Clinical Application

Kinetics of Nanomedicine in Tumor Spheroid as an In Vitro Model System for Efficient Tumor-Targeted Drug Delivery With Insights From Mathematical Models

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

Contact Info

Product

Resources

About