Preclinical Landscape in Cancer Research

Preclinical Cancer Landscape discusses the issues in preclinical-to-clinical translatability of molecularly targeted cancer therapies and the need to better align tumour biology in patients With a strong focus on the status, challenges, prospects and the need of robustness of preclinical cancer research, the book acknowledges that the bar for reproducibility in performing and presenting preclinical studies must be raised to facilitate a transparent discovery process that frequently and consistently leads to significant patient benefit. In 22 chapters this book describes the current status of preclinical research in multiple cancers. This book is a timely and valuable resource for health professionals, scientists and researchers, health practitioners, students, and all those who wish to broaden their knowledge in the allied field. " Preclinical landscape in cancer research " is written by experts in the field and informed with facts directly from manufacturers. Pharmaceutical scientists, medical researchers, biomedical engineers and clinical professionals will find this an essential reference.

Title of Book
Cover image
Title page
Table of Contents
Copyright
Contributors
About the editors
Preface
Drug Delivery Systems Landscape in Cancer Research (Vol. 1)
Biomarker Landscape in Cancer Research (Vol. 2)
Diagnostics Landscape in Cancer Research (Vol. 3)
Preclinical Landscape in Cancer Research (Vol. 4)
Clinical Landscape in Cancer Research (Vol. 5)
1. Liver cancer: Current status of preclinical research
Introduction
Liver cancer
Epidemiology of liver cancer
Epidemiology of HBV and HCV associated liver cancer
Epidemiology of alcohol-associated liver cancer
Epidemiology of NAFLD/NASH associated liver cancer
Cells of origin for the liver cancer
Hypothesizing the cells of origin of liver cancer
Immune response in the development of liver cancer
Currently used therapies for liver cancer
Current preclinical research and developments
Combination therapies
Drug repurposing
Small molecule inhibitors
Natural products used to treat liver cancer
Zebrafish models
Radiotherapy
Nanoparticle systems for targeted drug delivery
Three dimensional (3D) bioprinting and 3D organoids
Conclusion
2. Bone cancer: Current status in preclinical research
Introduction
Primary bone cancers
Osteocytes: A multipurpose, adaptable bone cell
RANK/RANKL/osteoprotegerin and Wnt signaling pathways
Bone metastasis
Animal models for bone cancer
B7–H3 and its role in bone cancers
Mammalian target of rapamycin (mTOR) pathway
Cytokines and bone tumors
Conclusion
3. Spleen cancer: Current status of preclinical research
Introduction
World statistics and factors affecting
Cellular mechanism
Preclinical reports in treating spleen cancer
Current marketed therapy
Drug discovery-new drugs tested in preclinical stage only
Preclinical studies on splenic lymphoma
Cell line models for spleen cancer
3D printing for spleen carcinoma
Lab on chip
Animal models
Zebrafish models of cancer
Other animal models
Murine model
Rabbit-model
Conclusion
4. Head and neck cancers: Current status preclinical research
Introduction
World statistics
Causative agents and impact of lifestyle changes
Cellular mechanisms
Current treatments for HNC
Preclinical in vitro cell line models
Cell line models
3D in vitro tumor models
Microfluidic Devices
In vivo models
Pharmacokinetic data
Future perspectives
Conclusion
5. Lung cancer: Current status of preclinical research
Introduction
Types of lung cancer
Preclinical landscape
Models in lung cancer research
In vitro cell line models
In vivo models
Ex vivo models
The importance of molecular profiling (IMP) in lung cancer
Correlation between drug delivery system and preclinical models
Targeted therapies and immunotherapies
EGFR-targeted therapies
KRAS-targeted therapies
Immunotherapies
Combination therapy
Emerging technologies in preclinical research
Genomics
Transcriptomics
Proteomics
Metabolomics
Animal models for drug testing
Challenges and future directions
Conclusion
6. Thyroid cancer: Current status of preclinical landscape
Introduction
Genetics and therapy
Diagnosis and prognosis
Intracellular mechanisms
Treatment of thyroid cancer
Current and novel pharmacological treatments
Tyrosine kinase inhibitor (TKI)
Anti-BRAF molecules
Anti-mTOR molecules
Drugs under clinical trials
Preclinical data and literature
Apoptosis enhancing strategies
Immunotherapy
Combination treatment
Cell line models
2D cell lines
3D cell lines
2D and 3D models in Coculture systems
Preclinical animal models
Requirements for preclinical (animal) model selection for thyroid cancer studies
Mice and xenograft models
Patient-derived xenograft models
Syngeneic models
Genetically engineered mouse model (GEMM)
Organ-on-chip technology
Preclinical models in thyroid cancer
Conclusion
7. Adrenal cancer: Current status of preclinical research
Introduction
Epidemiology and incidences
Etiology and risk factors of ACC
Clinical presentation of adrenocortical cancer
Staging of adrenal cancer
Prognosis
Current treatment approaches in ACC
Surgical management:
Systemic therapy:
Mitotane therapy:
Cytotoxic chemotherapy:
Targeted therapies:
Immunotherapy:
Local therapies:
Challenges in adrenocortical cancer management
Importance of preclinical studies
Pathogenesis and genetics
Genetic mutations associated with adrenal cancer
Germline mutations
Somatic mutations
Epigenetic changes and molecular classification
Deregulation of apoptosis in adrenocortical cancer
Preclinical models of adrenocortical cancer
In vitro models
2D cell cultures
Primary cell cultures
3D cell cultures
In vivo models
Xenograft models:
Establishment of xenograft models:
Genetically engineered mouse models (GEMMs)
Constitutively active β-catenin model [51]:
Simultaneous β-catenin activation and TP53 knock out [52]:
IGF2 overexpression model [53]:
ZNRF3 knockout model [54]:
Triple combination model:
CRISPR/Cas P gene editing:
High-throughput screening (HTS):
Proteomics and metabolomics:
Single-cell RNA sequencing:
Imaging techniques:
Bioluminescent and fluorescent imaging:
Humanized mouse models:
Combination with liquid biopsies for real-time monitoring:
Use of artificial intelligence (AI) with PDX models:
Pharmacological agents in preclinical studies
Targeted therapies in preclinical studies
Biomarkers of adrenocortical cancer
Clinical trials and future directions
Conclusion
8. Breast cancer: Current status of preclinical research
Introduction
World statistics
Factors affecting breast cancer
Cellular mechanism
Estrogen receptors (ER) signaling pathway
Human epidermal growth factor receptor (HER2) signaling pathway
Canonical Wnt/b-catenin signaling pathway
Notch signaling pathway
Sonic Hedgehog (SHH) signaling pathway
Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway
Preclinical breast cancer models
Current treatments
Drug discovery
Status of hormone receptors
New upcoming drugs
Cellular preclinical models
Phagocytic assay
Basement membrane crossing assay
Cell-line models available (2D/3D)
Ex-vivo models
3D printed breast models
Estimation of endogenous antioxidants
Animal model
Human breast cancer xenograft animal model
Conclusion
9. Colorectal cancer: Current status of preclinical research
Introduction
Epidemiology
Factors affecting incidence and mortality of CRC
Age
Gender
Race and ethnicity
Cellular mechanism behind colorectal cancer (CRC)
Genetic mutations
Alterations in signaling pathways
Preclinical landscape
Current marketed therapy
Preclinical models in CRC research
Cell line models
In vivo models
Ex vivo models
CRC treatment and preclinical research
Absorption, distribution, metabolism, and excretion
Clinical pharmacokinetic considerations
Local drug delivery
Toxicity management
Challenges of preclinical models
Animal models: Species and applications
Mice
Rats
Zebrafish
Regulatory guidelines for animal use
Future prospects of CRC preclinical research
Conclusion
10. Prostate cancer: Current status and preclinical research
Introduction
Biomarkers
Biomarker tests based on serum level sampling
Prostate-specific antigen (PSA)
4KS (4K-Score)
Prostate health index (PHI)
Biomarker tests based on tissue level sampling
Oncotype Dx
Confirm MDx
Decipher
Prolaris
Promark
Biomarker tests based on urine-level sampling
Progensa
My Prostate Score (MPS)
Select MDx
ExoDx
Preclinical research
Cellular based model
Androgen dependent cells
Androgen independent cells
Wild type-AR (WT-AR) cells
Typical RWPE-1 prostate epithelial cells
Primary tumor-derived PrC cell lines
Metastatic tumor-derived PrC cell lines
PrC cell lines resistance to chemotherapeutic drugs
Xenograft models for PrC
Cell derived xenograft models (PD-X)
Patient derived xenograft models (PD-X)
Transgenic models
The transgenic adenocarcinoma of the mouse prostate (TRAMP) model
Phosphatase and tensin homolog (PTN) knock-out model
Androgen receptor knockout (ARKO) mice model
Organ on a chip (O-oC) model for PrC
In vivo animal model
Mouse model
Rat model
Canine model
Ex vivo PrC models
Importance of pharmacokinetics in PrC
Impact of nanoparticles in PrC treatment
Conclusion
11. Ovarian cancer: Current status of preclinical research
Introduction
World statistics
Cellular mechanisms of ovarian cancer
Genetic mutations:
Tumor suppressors and oncogenes:
Epithelial–mesenchymal transition (EMT):
Angiogenesis:
Hormonal influences:
Immune system evasion:
Preclinical landscape
Current marketed therapy for ovarian cancer
Surgery:
Chemotherapy:
Targeted therapy:
Antiangiogenesis therapy:
Immunotherapy:
Maintenance therapy:
Alkeran (melphalan)
Alymsys (Bevacizumab)
Avastin (Bevacizumab)
Bevacizumab
Carboplatin
Cisplatin
Cyclophosphamide
Doxorubicin hydrochloride
Doxil (Doxorubicin Hydrochloride Liposome)
Doxorubicin Hydrochloride Liposome
Elahere (mirvetuximab soravtansine-gynx)
Gemcitabine hydrochloride
Gemzar (Gemcitabine hydrochloride)
Hycamtin (Topotecan hydrochloride)
Infugem (Gemcitabine hydrochloride)
Lynparza (Olaparib)
Melphalan
Mirvetuximab soravtansine-gynx
Mvasi (Bevacizumab)
Niraparib Tosylate monohydrate
Olaparib
Paclitaxel
Paraplatin (Carboplatin)
Rubraca (Rucaparib Camsylate)
Rucaparib Camsylate
Tepadina (Thiotepa)
Thiotepa
Topotecan hydrochloride
Zejula (Niraparib Tosylate monohydrate)
Zirabev (Bevacizumab)
Preclinical models for ovarian cancer
In vitro and ex vivo models
Established cancer-derived cell lines
Primary ovarian cancer cell lines
Two- and three-dimensional cell culture models
Organoids
Tumor-on-a-chip
In vivo models
Carcinogen-induced tumor models
Syngeneic models
Xenografts of established ovarian cancer cell lines
Patient-derived xenografts
Humanized mouse models
Genetically engineered mouse models
Laying hen model
Zebrafish model
2D and 3D modeling of ovarian cancer
2D cultures
3D cultures
Cancer spheroids
Hydrogel-based models
Organoids
Organotypic cultures
Scaffold-based organotypic cultures
Cancer-on-a-chip devices
Toxicity data
Platinum agents
Paclitaxel
Oral etoposide
Liposomal doxorubicin
Gemcitabine
Topotecan
Conclusion
12. Gastrointestinal cancer: Current status of preclinical research
Introduction
Epidemiology of gastrointestinal cancer
Risk factors and molecular mechanisms
Molecular pathways and targets
Signaling pathways
Immune microenvironment
Preclinical models
Types of preclinical models
Cancer cell line
Two-dimensional cell culture
Three-dimensional cell culture
Syngeneic mouse models
Patient-derived xenograft
Patient-derived organoid model
Gastrointestinal organoids
Multicellular PDO models
PDO/immune cell cocultures
PDO/CAF cocultures
Organoid-on-a-chip
Gastrointestinal organoids-on-a-chip models
Emerging therapeutic strategies
Surgery
Chemotherapy
Targeted therapies
HER2 targeted therapy
Claudin targeted therapy
Peptide-based targeted therapy
Immunotherapy
Phyto therapy
Conclusion
13. Oral cancer: Current status of preclinical research
Introduction
Management of oral cancer
Preclinical landscape in oral cancer
Local delivery
Pharmacokinetic models
Conventional methods and microfluidic approaches in cancer diagnosis and treatment
In vitro cell, in vivo, and ex vivo models
Current treatment option
VEGF inhibitors
FGFR inhibitors
EGFR inhibitors
mTOR inhibitors
AKT inhibitors
MEK and ERK inhibitors
JAK/STAT inhibitors
CDK4/6 inhibitors
c-MET inhibitors
Novel inhibitors under study
Organ-on-chip
Conclusion
14. Ocular cancer: Current status of preclinical research
Introduction
World statistics
Cellular mechanism
Preclinical landscape
Drug discovery – preclinical research for ocular cancer
Tebentafusp
Ipilimumab
Current treatment options
Preclinical study models
Cellular model
Ex vivo model
Animal models
Conclusion
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Preclinical Landscape in Cancer Research

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Ranjita Shegokar

Yashwant Pathak

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