3D collagen fibrillar microstructure guides pancreatic cancer cell phenotype ...Arun kumar
Pancreatic cancer, one of the deadliest cancers, is characterized by high rates of metastasis
and intense desmoplasia, both of which are associated with changes in fibrillar type I collagen
composition and microstructure. Epithelial to mesenchymal transition (EMT), a critical
step of metastasis, also involves a change in extracellular matrix (ECM) context as cells
detach from basement membrane (BM) and engage interstitial matrix (IM). The objective of
this work was to develop and apply an in-vitro three-dimensional (3D) tumor-ECM model to
define how ECM composition and biophysical properties modulate pancreatic cancer EMT.
Three established pancreatic ductal adenocarcinoma (PDAC) lines were embedded within
3D matrices prepared with type I collagen Oligomer (IM) at various fibril densities to control
matrix stiffness or Oligomer and Matrigel combined at various ratios while maintaining constant
matrix stiffness
From 3D Cell Culture System to Personalized Medicine in Osteosarcoma_Crimson ...CrimsonpublishersITERM
Osteosarcoma is the most common primary bone malignancy presenting typically during childhood and adolescence. However, few improvements of the survival outcomes for osteosarcoma patients have been achieved since the last three decades. Despite the rarity of the diagnosis, the complexity of tumor microenvironment and the genetic heterogeneity of osteosarcoma remain the major obstacles to understanding the mechanisms involved in tumor progression and metastasis, and to screening the pharmacologically active molecules for better drugs. Compared to the 2D cell culture system, 3D cell culture system is much closer to the in vivo physiological condition in tumor. Thus, 3D cell culture system could be a powerful technique to screen therapeutic agent towards personalized medicine in osteosarcoma.
3D collagen fibrillar microstructure guides pancreatic cancer cell phenotype ...Arun kumar
Pancreatic cancer, one of the deadliest cancers, is characterized by high rates of metastasis
and intense desmoplasia, both of which are associated with changes in fibrillar type I collagen
composition and microstructure. Epithelial to mesenchymal transition (EMT), a critical
step of metastasis, also involves a change in extracellular matrix (ECM) context as cells
detach from basement membrane (BM) and engage interstitial matrix (IM). The objective of
this work was to develop and apply an in-vitro three-dimensional (3D) tumor-ECM model to
define how ECM composition and biophysical properties modulate pancreatic cancer EMT.
Three established pancreatic ductal adenocarcinoma (PDAC) lines were embedded within
3D matrices prepared with type I collagen Oligomer (IM) at various fibril densities to control
matrix stiffness or Oligomer and Matrigel combined at various ratios while maintaining constant
matrix stiffness
From 3D Cell Culture System to Personalized Medicine in Osteosarcoma_Crimson ...CrimsonpublishersITERM
Osteosarcoma is the most common primary bone malignancy presenting typically during childhood and adolescence. However, few improvements of the survival outcomes for osteosarcoma patients have been achieved since the last three decades. Despite the rarity of the diagnosis, the complexity of tumor microenvironment and the genetic heterogeneity of osteosarcoma remain the major obstacles to understanding the mechanisms involved in tumor progression and metastasis, and to screening the pharmacologically active molecules for better drugs. Compared to the 2D cell culture system, 3D cell culture system is much closer to the in vivo physiological condition in tumor. Thus, 3D cell culture system could be a powerful technique to screen therapeutic agent towards personalized medicine in osteosarcoma.
HDAC4 and HDAC7 Promote Breast and Ovarian Cancer Cell Migration by Regulatin...CrimsonpublishersCancer
Breast and ovarian cancer have been remained as a highly malignant tumor among women, posing a serious threat to women health worldwide. In this study, we were aimed to investigate the underlying mechanism of breast and ovarian cancer cell migration. Wound healing assay showed that MDA-MB-231and C13* have higher migration potential compare with MCF-7 and OV2078 cells, as well as regulated epithelial-mesenchymal transition (EMT) marker. We found that HDAC4 and HADC7 mRNA are up regulated in MDA-MB-231 and C13* cells. Moreover, target HDAC4 and HDAC7 by TSA or shRNA block MDA-MB-231and C13* migration. These results reveal a new link between HDACs and EMT in the regulation of breast and ovarian cancer migration.
Potentials of 3D models in anticancer drug screeningAnjali R.
A short presentation about the differences between 2D and 3D culture models, why researchers are moving toward 3D models in anticancer drug screening, the methods used in doing so and a recent case study of 3D tumour model being used for drug screening.
REVIEWCancer stem cells a new framework for the designo.docxjoellemurphey
REVIEW
Cancer stem cells: a new framework for the design
of tumor therapies
Boyan K. Garvalov & Till Acker
Received: 14 July 2010 /Revised: 27 August 2010 /Accepted: 16 September 2010
# Springer-Verlag 2010
Abstract Modern tumor therapy has achieved considerable
progress, but many tumors remain refractory to treatment or
relapse following initial remission. Recent evidence points
to one possible reason for this limited therapeutic efficiency:
that the design of anticancer agents so far may not have been
aimed at the right target. While conventional tumor therapies
have targeted the main mass of tumor cells, there is now
compelling evidence that tumor initiation and progression are
driven by a subpopulation of tumor cells that possess stem cell
properties and are resistant to traditional cancer treatments—
the cancer stem cells (CSCs). CSCs have been identified in
most types of cancer and can be separated from the rest of the
tumor cells using appropriate markers. CSCs are regulated by
molecular mechanisms and specific, perivascular, and hypox-
ic microenvironments, which largely overlap with those
controlling stem cells from normal tissues. Our improved
understanding of CSC biology has already provided a number
of novel targets and drug discovery platforms for the design of
specific therapies that aim to eradicate the CSC subpopula-
tion. Therapeutic approaches can be targeted either at
eliminating the CSCs themselves or at disrupting the niches
in which CSCs reside. Moreover, the importance of CSCs for
tumor growth, resistance, and progression implies that clinical
trials and preclinical studies of anticancer therapies should
include as a key element an assessment of the abundance and
persistence of CSCs. Thus, CSC research holds great promise
for providing important new impetus to the fields of tumor
biology and clinical oncology.
Keywords Cancer stem cell . Hypoxia .
Microenvironment . Angiogenesis . Antitumor therapy.
Metastasis
The hierarchy model and cancer stem cells (CSCs)
The classical view of tumor formation is based on the
“stochastic” or “clonal evolution” model [1, 2]. It perceives
the tumor as a mass of hyperproliferative cells with similar
potential for driving tumor growth. Tumor heterogeneity
and progression are seen as the result of variations in the
tumor microenvironment and genetic mutations in individ-
ual cells, followed by selection of those that are best
adapted to support the further growth of the tumor (Fig. 1a).
An alternative concept that has been gaining increasing
experimental support is the “hierarchy” or “cancer stem
cell” model [3]. This model posits that tumors are generated
and maintained in a manner similar to the physiological
stem cell system operating in normal tissues, i.e., by cells
with stem cell-like properties, which self-renew and
differentiate into the distinct cellular subtypes of the tumor
(Fig. 1b). The key novel features of this model are that only
a limited population of tumor cell ...
A physical sciences network characterization of non-tumorigenic and metastati...Shashaanka Ashili
To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the
Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic DA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells’ regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.
Cyclic Peptides Current Status & Future Prospects.pdfDoriaFang
Researchers have made unremitting efforts to optimize peptides in order to improve the bioavailability of peptide drugs. Cyclization of peptides is one of the methods to optimize peptides. Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics.
Antibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdfDoriaFang
Summary of Antibody–Oligonucleotide Conjugates(AOCs) in Clinical Trials, including products from Avidity Biosciences, Dyne Therapeutics, Tallac Therapeutics and Denali Therapeutics.
More Related Content
Similar to 3D Bioprinted Cancer Models Advantages, Roles & Applications In Drug Development.pdf
HDAC4 and HDAC7 Promote Breast and Ovarian Cancer Cell Migration by Regulatin...CrimsonpublishersCancer
Breast and ovarian cancer have been remained as a highly malignant tumor among women, posing a serious threat to women health worldwide. In this study, we were aimed to investigate the underlying mechanism of breast and ovarian cancer cell migration. Wound healing assay showed that MDA-MB-231and C13* have higher migration potential compare with MCF-7 and OV2078 cells, as well as regulated epithelial-mesenchymal transition (EMT) marker. We found that HDAC4 and HADC7 mRNA are up regulated in MDA-MB-231 and C13* cells. Moreover, target HDAC4 and HDAC7 by TSA or shRNA block MDA-MB-231and C13* migration. These results reveal a new link between HDACs and EMT in the regulation of breast and ovarian cancer migration.
Potentials of 3D models in anticancer drug screeningAnjali R.
A short presentation about the differences between 2D and 3D culture models, why researchers are moving toward 3D models in anticancer drug screening, the methods used in doing so and a recent case study of 3D tumour model being used for drug screening.
REVIEWCancer stem cells a new framework for the designo.docxjoellemurphey
REVIEW
Cancer stem cells: a new framework for the design
of tumor therapies
Boyan K. Garvalov & Till Acker
Received: 14 July 2010 /Revised: 27 August 2010 /Accepted: 16 September 2010
# Springer-Verlag 2010
Abstract Modern tumor therapy has achieved considerable
progress, but many tumors remain refractory to treatment or
relapse following initial remission. Recent evidence points
to one possible reason for this limited therapeutic efficiency:
that the design of anticancer agents so far may not have been
aimed at the right target. While conventional tumor therapies
have targeted the main mass of tumor cells, there is now
compelling evidence that tumor initiation and progression are
driven by a subpopulation of tumor cells that possess stem cell
properties and are resistant to traditional cancer treatments—
the cancer stem cells (CSCs). CSCs have been identified in
most types of cancer and can be separated from the rest of the
tumor cells using appropriate markers. CSCs are regulated by
molecular mechanisms and specific, perivascular, and hypox-
ic microenvironments, which largely overlap with those
controlling stem cells from normal tissues. Our improved
understanding of CSC biology has already provided a number
of novel targets and drug discovery platforms for the design of
specific therapies that aim to eradicate the CSC subpopula-
tion. Therapeutic approaches can be targeted either at
eliminating the CSCs themselves or at disrupting the niches
in which CSCs reside. Moreover, the importance of CSCs for
tumor growth, resistance, and progression implies that clinical
trials and preclinical studies of anticancer therapies should
include as a key element an assessment of the abundance and
persistence of CSCs. Thus, CSC research holds great promise
for providing important new impetus to the fields of tumor
biology and clinical oncology.
Keywords Cancer stem cell . Hypoxia .
Microenvironment . Angiogenesis . Antitumor therapy.
Metastasis
The hierarchy model and cancer stem cells (CSCs)
The classical view of tumor formation is based on the
“stochastic” or “clonal evolution” model [1, 2]. It perceives
the tumor as a mass of hyperproliferative cells with similar
potential for driving tumor growth. Tumor heterogeneity
and progression are seen as the result of variations in the
tumor microenvironment and genetic mutations in individ-
ual cells, followed by selection of those that are best
adapted to support the further growth of the tumor (Fig. 1a).
An alternative concept that has been gaining increasing
experimental support is the “hierarchy” or “cancer stem
cell” model [3]. This model posits that tumors are generated
and maintained in a manner similar to the physiological
stem cell system operating in normal tissues, i.e., by cells
with stem cell-like properties, which self-renew and
differentiate into the distinct cellular subtypes of the tumor
(Fig. 1b). The key novel features of this model are that only
a limited population of tumor cell ...
A physical sciences network characterization of non-tumorigenic and metastati...Shashaanka Ashili
To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the
Physical Sciences–Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic DA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells’ regulatory networks involved in morphology and survival. These results provide a multifaceted description of cellular parameters of two widely used cell lines and demonstrate the value of the PS-OC Network approach for integration of diverse experimental observations to elucidate the phenotypes associated with cancer metastasis.
Similar to 3D Bioprinted Cancer Models Advantages, Roles & Applications In Drug Development.pdf (20)
Cyclic Peptides Current Status & Future Prospects.pdfDoriaFang
Researchers have made unremitting efforts to optimize peptides in order to improve the bioavailability of peptide drugs. Cyclization of peptides is one of the methods to optimize peptides. Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics.
Antibody–Oligonucleotide Conjugates (AOCs) in Clinical Trials.pdfDoriaFang
Summary of Antibody–Oligonucleotide Conjugates(AOCs) in Clinical Trials, including products from Avidity Biosciences, Dyne Therapeutics, Tallac Therapeutics and Denali Therapeutics.
Alzheimer's Disease Drug Development Aducanumab, Lecanemab & Donanemab.pdfDoriaFang
Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive and behavioral impairment. Here we introduce the development of AD drugs (Aducanumab, Lecanemab & Donanemab).
Summary of Targeted Protein Degradation in Clinical Trials.pdfDoriaFang
Summary of targeted protein degradation, such as PROTAC and molecular glues in clinical trials. PROTAC and molecular glues are the two main modes of TPD technology based on the UPS.
Cleavable Linkers Used In ADC Development.pdfDoriaFang
The linker used in ADC is divided into two types: cleavable linker and non-cleavable linker. This artile mainly introduced the cleavable linkers used in ADC development.
The Role of Four Lipid Components Of LNPs.pdfDoriaFang
LNP consists of four components: ionizable cationic lipids, phospholipids, cholesterol, and PEG lipids. Each component plays a key role in terms of LNP preparations.
Trophoblast Glycoprotein (TPGB5T4) A New Target For ADC Drugs.pdfDoriaFang
The more popular targets in ADC drugs include HER2, TROP2, EGFR, CLDN18.2, c-Met, CD19, PSMA, Muc1, BCMA and PDL1. Here we will introduce a new ADC target trophoblast glycoprotein (TPBG).
Similar to HER2, Trop-2 is a new hot target for research. Trodelvy has been one of the products receiving much attention in recent years, and Dato-DXd from AstraZeneca/Daiichi Sankyo is also advancing rapidly.
DS-8201 (Enhertu) A Potential ADC Drug Targeting HER2.pdfDoriaFang
Enhertu (fam-Trastuzumab deruxtecan-nxki) is a HER2-targeting ADC drug jointly developed by AstraZeneca and Daiichi Sankyo, also known as DS-8201 or T-DXd.
List of New Anti-cancer Drugs Approved By FDA In The First Half of 2023.pdfDoriaFang
What are the new anti-cancer drugs approved in the first half of the year? The new drugs approved covered a variety of solid tumors and blood tumor types.
Summary of ADC Targets For Solid Tumors & Hematological Tumors.pdfDoriaFang
Currently, popular targets include CD family, BCMA, HER2, TROP2, Tissue factor, Nectin-4, FRα, EGFR, etc. Here, we briefly introduce ADC targets in solid tumors and hematological tumors.
New Oncology Trends ADCs, Bispecific Antibodies & CAR-T Cell.pdfDoriaFang
Scientists are turning their attention to more innovative therapeutic strategies, such as next-generation ADCs, bispecific antibodies and CAR-T cell therapies, etc. as cancer therapy.
Summary of Treatments for Multiple Myeloma.pdfDoriaFang
Currently, there are a variety of drugs available for multiple myeloma, including traditional cytotoxic drugs, immunomodulatory analogs, proteasome inhibitors, antibody-based drugs and CAR T-cell therapy.
Buy Verified PayPal Account | Buy Google 5 Star Reviewsusawebmarket
Buy Verified PayPal Account
Looking to buy verified PayPal accounts? Discover 7 expert tips for safely purchasing a verified PayPal account in 2024. Ensure security and reliability for your transactions.
PayPal Services Features-
🟢 Email Access
🟢 Bank Added
🟢 Card Verified
🟢 Full SSN Provided
🟢 Phone Number Access
🟢 Driving License Copy
🟢 Fasted Delivery
Client Satisfaction is Our First priority. Our services is very appropriate to buy. We assume that the first-rate way to purchase our offerings is to order on the website. If you have any worry in our cooperation usually You can order us on Skype or Telegram.
24/7 Hours Reply/Please Contact
usawebmarketEmail: support@usawebmarket.com
Skype: usawebmarket
Telegram: @usawebmarket
WhatsApp: +1(218) 203-5951
USA WEB MARKET is the Best Verified PayPal, Payoneer, Cash App, Skrill, Neteller, Stripe Account and SEO, SMM Service provider.100%Satisfection granted.100% replacement Granted.
The world of search engine optimization (SEO) is buzzing with discussions after Google confirmed that around 2,500 leaked internal documents related to its Search feature are indeed authentic. The revelation has sparked significant concerns within the SEO community. The leaked documents were initially reported by SEO experts Rand Fishkin and Mike King, igniting widespread analysis and discourse. For More Info:- https://news.arihantwebtech.com/search-disrupted-googles-leaked-documents-rock-the-seo-world/
Recruiting in the Digital Age: A Social Media MasterclassLuanWise
In this masterclass, presented at the Global HR Summit on 5th June 2024, Luan Wise explored the essential features of social media platforms that support talent acquisition, including LinkedIn, Facebook, Instagram, X (formerly Twitter) and TikTok.
Digital Transformation and IT Strategy Toolkit and TemplatesAurelien Domont, MBA
This Digital Transformation and IT Strategy Toolkit was created by ex-McKinsey, Deloitte and BCG Management Consultants, after more than 5,000 hours of work. It is considered the world's best & most comprehensive Digital Transformation and IT Strategy Toolkit. It includes all the Frameworks, Best Practices & Templates required to successfully undertake the Digital Transformation of your organization and define a robust IT Strategy.
Editable Toolkit to help you reuse our content: 700 Powerpoint slides | 35 Excel sheets | 84 minutes of Video training
This PowerPoint presentation is only a small preview of our Toolkits. For more details, visit www.domontconsulting.com
Top mailing list providers in the USA.pptxJeremyPeirce1
Discover the top mailing list providers in the USA, offering targeted lists, segmentation, and analytics to optimize your marketing campaigns and drive engagement.
Premium MEAN Stack Development Solutions for Modern BusinessesSynapseIndia
Stay ahead of the curve with our premium MEAN Stack Development Solutions. Our expert developers utilize MongoDB, Express.js, AngularJS, and Node.js to create modern and responsive web applications. Trust us for cutting-edge solutions that drive your business growth and success.
Know more: https://www.synapseindia.com/technology/mean-stack-development-company.html
3.0 Project 2_ Developing My Brand Identity Kit.pptxtanyjahb
A personal brand exploration presentation summarizes an individual's unique qualities and goals, covering strengths, values, passions, and target audience. It helps individuals understand what makes them stand out, their desired image, and how they aim to achieve it.
In the Adani-Hindenburg case, what is SEBI investigating.pptxAdani case
Adani SEBI investigation revealed that the latter had sought information from five foreign jurisdictions concerning the holdings of the firm’s foreign portfolio investors (FPIs) in relation to the alleged violations of the MPS Regulations. Nevertheless, the economic interest of the twelve FPIs based in tax haven jurisdictions still needs to be determined. The Adani Group firms classed these FPIs as public shareholders. According to Hindenburg, FPIs were used to get around regulatory standards.
Building Your Employer Brand with Social MediaLuanWise
Presented at The Global HR Summit, 6th June 2024
In this keynote, Luan Wise will provide invaluable insights to elevate your employer brand on social media platforms including LinkedIn, Facebook, Instagram, X (formerly Twitter) and TikTok. You'll learn how compelling content can authentically showcase your company culture, values, and employee experiences to support your talent acquisition and retention objectives. Additionally, you'll understand the power of employee advocacy to amplify reach and engagement – helping to position your organization as an employer of choice in today's competitive talent landscape.
Putting the SPARK into Virtual Training.pptxCynthia Clay
This 60-minute webinar, sponsored by Adobe, was delivered for the Training Mag Network. It explored the five elements of SPARK: Storytelling, Purpose, Action, Relationships, and Kudos. Knowing how to tell a well-structured story is key to building long-term memory. Stating a clear purpose that doesn't take away from the discovery learning process is critical. Ensuring that people move from theory to practical application is imperative. Creating strong social learning is the key to commitment and engagement. Validating and affirming participants' comments is the way to create a positive learning environment.
Discover the innovative and creative projects that highlight my journey throu...dylandmeas
Discover the innovative and creative projects that highlight my journey through Full Sail University. Below, you’ll find a collection of my work showcasing my skills and expertise in digital marketing, event planning, and media production.
Discover the innovative and creative projects that highlight my journey throu...
3D Bioprinted Cancer Models Advantages, Roles & Applications In Drug Development.pdf
1. Biopharma PEG https://www.biochempeg.com
3D Bioprinted Cancer Models: Advantages,
Roles & Applications In Drug Development
Currently, efforts invested in developing new drugs often fail to translate into meaningful
clinical benefits for cancer patients. Therefore, developing more effective anticancer
therapies and accurately predicting their clinical value remains an urgent medical need.
Because solid cancers have complex and heterogeneous structures composed of
different cell types and extracellular matrices, three-dimensional (3D) cancer models
have great potential to advance our understanding of cancer
biology.
Advanced 3D bioprinted cancer models have the potential to revolutionize the way we
discover therapeutic targets, develop new drugs, and personalize anticancer treatments in
an accurate, reproducible, clinically transferable and robust manner. Therefore, it is
critical to gain insight into the differences in tumorigenesis between 2D, 3D, and tumor
animal models, and this emerging field will contribute to current cancer research as well
as clinical translation of new therapies.
Advantages of 3D Bioprinted Cancer Models
2. Biopharma PEG https://www.biochempeg.com
An ideal 3D bioprinted cancer model can precisely reproduce the in vivo
environment of a specific tumor, including its perfusion vessels. This enables
multiple biochemical assessments of tumor cell behavior that mimic the in vivo
environment. Indeed, gene expression analysis showed that compared with 2D cultures,
3D bioprinted cancer models could show immunoglobulin production, expression of
proinflammatory molecules, activation of cytokines and/or chemokines, upregulation of
cell-cell adhesion pathways, and reduction of proteins associated with cell division and
DNA replication. These differences provide insights into how the 3D environment affects
cancer cell growth, migration, invasion, stem cells, and gene expression.
In addition, the elasticity, plasticity, and mechanical properties of the original tumor ECM
can be modeled by using specific matrix materials. For example, hepatogenic
decellularized ECM and mammary decellularized ECM have retained microstructures and
3. Biopharma PEG https://www.biochempeg.com
ultrastructures that, together with growth factors bound and sequestered in the matrix,
control cell location and orientation. The decellularized ECM scaffolds printed by digital
light processing (DLP) technology enable accurate spatial cell deposition, thereby
preserving these tissue-specific growth factors. DLP-based models have also been used
to study the initial stages of pancreatic ductal adenocarcinoma development.
Blood vessels play a crucial role in tumor proliferation, oxygen diffusion, angiogenesis,
endovascular and extravasation. Therefore, the realization of functional vascular networks
in biomimetic tumor models is essential to maintain cell viability and reveal the close
relationship between tumor and blood vessels. This dynamic environment can be studied
by 3D bioprinted cancer models containing vasculature, including how circulating cancer
cells interact with stromal cells and infiltrating immune cells, the exchange of secreted
factors between different cell types, the response to external stimuli, and the behavioral
adaptation of cancer cells to the metastatic microenvironment.
Each cancer has a unique TME that includes various healthy functional cell types, such as
stromal cells, vascular cells, and immune cells. However, non-bioprinted 3D cancer
models, which are implemented by means of structures such as hydrogel constructs,
polymer scaffolds, microcarrier beads, and hanging droplets, do not allow spatiotemporal
control of tissue formation and do not allow long-term observation of dynamic changes.
3D bioprinted models can overcome these limitations by reconstructing the entire TME,
including its functional and structural hierarchies, thus faithfully mimicking the complex in
vivo tumor tissue structure at high resolution and maintaining the viability and function of
patient-derived tissue.
The Important Role of 3D Bioprinted Cancer
Models
Simulating a Metastatic Niche
4. Biopharma PEG https://www.biochempeg.com
An important challenge in cancer research is to construct in vitro models that can
reproduce natural metastatic niches. In addition to differences in ECM properties between
metastatic sites, the interaction between invading cancer cells and the TME within the
metastatic niche is critical in mediating the metastatic cascade.
In a 3D bioprinted model simulating the bone metastatic niche, MDA-MB-231 breast
cancer cells were co-cultured with osteoblasts and human bone marrow mesenchymal
stem cells (MSCs) to mimic the bone TME. The proliferation rate of MSCs and osteoblasts
decreased within 5 days after the addition of cancer cells, suggesting that breast cancer
cells induce osteolysis in tumor bone. In addition, breast cancer cells in this model
showed increased secretion of the proangiogenic factor VEGF and decreased alkaline
phosphatase activity, which are markers of new bone formation.
Simulating tumor blood vessel
Improved understanding of tumor cell-endothelial cell interactions could reveal important
mechanisms of tumor metastasis and angiogenesis. By 3D bioprinting, breast cancer
microspheres were generated, which encapsulated microfibers containing human
umbilical vein endothelial cells (HUVEC). When co-cultured with breast cancer cells,
HUVEC elongates toward cancer cells outside the fibers, which remain exclusively within
the fibers and form vascular-like cavities within the fibers. This finding shows the potential
of co-cultured 3D bioprinted cancer models to reshape the interaction between cancer
cells and endothelial cells.
Anti-tumor immunity
Bringing immune cells from the TME and periphery into 3D bioprinted models can provide
a reproducible platform to study human anticancer immune responses, thereby
generating tumor models suitable for understanding tumor biology and drug testing. For
example, in a 3D bioprinted model consisting of bladder cancer cells, fibroblasts, HUVEC,
5. Biopharma PEG https://www.biochempeg.com
and monocytes, treatment with Bacille Calmette-Guerin (BCG) resulted in increased
monocyte proinflammatory cytokine secretion and decreased cancer cell growth.
Currently, several 3D bioprinted models have been developed to rapidly and reliably
evaluate the efficacy of immune modulators and cell-based cancer immunotherapies. For
example, 3D bioprinted models have been used to evaluate chimeric antigen receptor
(CAR) T-cell therapy for neuroblastoma.
Brain malignancies face considerable therapeutic challenges, in part because of their
unique brain TMEs that promote tumor progression. A DLP-based 3D bioprinted
glioblastoma model has been developed that mimics the brain TME and contains glioma
stem cells, astrocytes, neural precursor cells, and macrophages. The model is also
capable of analyzing macrophage phenotypes and detecting multiple transcriptional
changes that occur as a result of cancer cells interacting with the TME. In this model,
macrophages recruited by cancer cells acquire a glioma-associated phenotype that
promotes tumorigenesis.
By combining different technologies and tuning the desired tissue-like properties and
cellular components, 3D bioprinted models can serve as valuable tools for studying TME
and cancer immunology.
Drug Development Applications of 3D
Bioprinted Cancer Models
3D bioprinting enables the assembly of cells and ECMs to form 3D constructs that
demonstrate the complexity of cancer tissues and serve as a robust and reproducible
platform for the discovery of new therapeutic targets, preclinical testing of anticancer
drugs, and the development of personalized cancer therapies.
6. Biopharma PEG https://www.biochempeg.com
Drug Efficacy Evaluation
3D-printed biological cancer models have been used in the screening and discovery of a
variety of drugs. ECM properties, such as density and composition, influence drug spread
and tumor penetration, and some 3D bioprinted tumor models take these factors into
account. In an iterative 3D bioprinting approach using GP-118 patient-derived gastric
adenocarcinoma cells suspended in a gelatin-alginate-matrix biomaterial, this 3D
bioprinted gastric adenocarcinoma model is chemo-resistant to Docetaxel, 5-fluorouracil,
and cisplatin and can be used to assess resistance to developing drugs.
3D bioprinted models have also been used to evaluate the therapeutic effects of
monoclonal antibodies. For example, metuzumab, an anti-CD174 antibody used to treat a
variety of cancers, researchers used heat-sensitive biomaterials to 3D bioprint
microfluidics composed of SMMC-7721 liver cancer cells and HUVECs. Higher doses of
metuzumab were required to inhibit cancer cell migration and proliferation in 3D models
7. Biopharma PEG https://www.biochempeg.com
compared with 2D cultures. Additionally, the incorporation of human peripheral blood
mononuclear cells into the 3D bioprinted model allowed the investigators to assess
metuzumab-induced ADCC cytotoxicity, an important aspect of therapeutic antibodies.
Drug screening platform
In addition to evaluating tumor response to drugs, 3D bioprinting platforms can help
high-throughput screening of compounds and approval of drugs for different diseases or
indications. Whole exome sequencing (WES) can identify the mutation profiles of patient
cancer samples and predict drug sensitivity by associating these profiles with specific
drugs that target mutations.
Target Discovery
The addition of perfusable vascular systems to multicellular 3D bioprinted models may
further improve drug screening platforms. For example, a 3D bioprinted microengineered
glioblastoma model is being developed that contains perfusable capillaries lined with
endothelial and pericytes and connected to a peripheral blood pump. This 3D model can
reflect the heterogeneity of glioblastoma samples, and the tumor cells in this 3D model are
transcriptionally more similar to in vivo glioblastoma tumor cells than 2D cultures derived
from the same cells. Notably, this model shows upregulation of P-selectin, whereas
glioblastoma cells grown in 2D medium do not express P-selectin and are not affected by
P-selectin inhibitors, suggesting that the use of 3D bioprinted cancer models may reveal
therapeutic targets that cannot be detected by conventional 2D culture.
In conclusion, 3D bioprinted cancer models have been shown to better reflect tumor
heterogeneity, TME complexity, cancer cell behavior, gene expression signatures, and
drug response than traditional 2D culture methods. These models also provide a platform
for studying parameters of cancer therapeutic approaches that cannot be adequately
studied using conventional 2D culture methods or simple 3D models.
8. Biopharma PEG https://www.biochempeg.com
Clinical Trials
Various ongoing clinical trials are evaluating the predictive power of 3D cancer models for
drug screening, target discovery, and personalized therapy. For example, an ongoing
clinical trial is evaluating 3D bioprinted liver cancer models to predict the response of
chemotherapy to colorectal cancer as well as liver metastases from colorectal cancer
(NCT04755907). Another trial uses 3D bioprinting of hyaluronic acid-gelatin biomaterials
to create organ-like models of myeloma (NCT03890614) and aims to create
patient-specific bioimprinted models to study myeloma biology and chemotherapy
sensitivity. These clinical studies provide proof of concept for the feasibility of using 3D
bioprinted cancer models to accurately model patient tumors and their dynamic
microenvironment and predict treatment outcomes.
Conclusion
3D bioprinted cancer models have the potential to transform the way we study, diagnose,
prevent and treat cancer. The commercialization of these models, especially in drug
development and testing, is expected to yield substantial economic benefits. In addition,
advanced 3D bioprinting technologies, combined with machine learning and AI-based
omics approaches, may uncover fundamental mechanisms of cancer biology, reveal
novel biomarkers and drug targets, and advance the development of effective
personalized cancer treatments. develop.
As a leading PEG supplier, Biopharma PEG specializes exclusively in the development
and manufacturing of high-quality PEG products and derivatives. We
supply AC-PEG-AC, AC-PEG-RGD and 8-ArmPEG-AC which can used in 3D bioprinting.
PEG-based hydrogels are most used polymers in the 3D printing techniques due to their
good biocompatibility in both in vitro and in vivo conditions. We can also
supply 4-ArmPEG-SG, 4-ArmPEG-SS, 8-ArmPEG-SG and 8-ArmPEG-SS which can be
9. Biopharma PEG https://www.biochempeg.com
used to crosslink into degradable PEG hydrogels.
Reference:
[1]. 3D bioprinted cancer models: from basic biology to drug development. Nat Rev
Cancer.2022 Oct 24.
Related articles:
[1]. Strategies Of Oral Drug Delivery: From Prodrug, Nanoparticles to 3D Printing
[2]. Polyethylene Glycol (PEG) Hydrogel Based 3D Bioprinting
[3]. A Covalently Crosslinked Bioink Used In Three-dimensional Cell Cultures of 3D
Bioprinting
[4]. The Role of PEGylated Materials In 3D Bioprinting