Combinational Therapy in Triple Negative Breast Cancer discusses TNBC at the molecular level from a holistic approach, focusing on combinational strategies targeting various pathways involved in this specific cancer type. Using a monotherapy for the treatment of cancer, especially high-grade tumors like TNBC, is mostly worthless due to the inherent genetic instability of tumor cells to develop intrinsic and acquired resistance. Combination therapy presents more, or at least the same, effectiveness with lower doses of every single agent and decreases the likelihood of chemoresistance, making it essential to understand for multiple therapy options.
The book is a valuable resource for cancer researchers, oncologists, graduate students and members of the biomedical field who are interested in the potential of combinational therapies to treat triple negative breast cancer.
Author(s): Manzoor Ahmad Mir
Publisher: Academic Press
Year: 2022
Language: English
Pages: 259
City: London
Contents
About the author
Foreword
Acknowledgment
Preface
Contributors
Chapter
1 - Triple-negative breast cancer - an aggressive subtype of breast cancer
Introduction
Triple-negative breast cancer (TNBC)
TNBC histological classification
TNBC molecular classification
BL-1 and BL-2
M subtype
MSL subtype
IM subtype
LAR subtype
TNBC and BRCA
Triple-negative breast cancer risk factors and epidemiology
Current diagnostic options for triple-negative breast cancer
Mammography
Ultrasound
Magnetic resonance imaging (MRI)
Future diagnostic options for TNBC
Blood-based liquid biopsy
Circulating tumor nucleic acids (ctNAs)
Exosomes
Immuno-positron emission tomography (PET)
Nanobiosensor
nCounter breast cancer 360 panel
Digital polymerase chain reaction (dPCR)
Triple-negative breast cancer’s prognostic implications
Somatic genomic mutations in TNBC
Epigenetic modifications in TNBC
Methylation of DNA in triple-negative breast cancer
Relation between DNA methylation and TNBC progression
Role of long noncoding RNAs in TNBC
Role of MicroRNA in TNBC
Role of histone modifications in TNBC
Summary
References
Chapter
2 - Novel biomarkers in triple-negative breast cancer - role and perspective
Introduction
Triple-negative breast cancer: Genetic markers
TP53
BRCA1/2
PI3K pathway
Androgen receptor
BCL2 gene
Cyclin-dependent kinases
Triple-negative breast cancer: Novel biomarkers
EGFR
VEGF
C-kit and basal cytokeratins
TOP-2A
Ki67
PARP
Heat shock protein 90
Cox-2
Epigenetic modifications in TNBC as novel biomarkers
Tissue miRNAs as biomarkers in TNBC
Circulating miRNAs as TNBC biomarkers
Novel developments in circulating miRNAs as diagnostic biomarkers for TNBC
LncRNAs as potential TNBC biomarkers
Targeted antibody–drug conjugates: Protein markers in TNBC
Immunotherapy biomarkers in TNBC
PDL1 and TILs
Tumor mutational burden as a biomarker
Summary
References
Chapter
3 - Current therapeutics and treatment options in TNBC
Introduction
Signaling pathways involved in triple-negative breast cancer (TNBC) treatment
Notch signaling pathway
Hedgehog signaling pathway
Wnt/β-catenin pathway
Mammalian target of rapamycin (mTOR) pathway
Poly (ADP-ribose) polymerase (PARP)
Epidermal growth factor receptor (EGFR)
TGF-β signaling pathway
CSPG4 protein signaling pathway
Role of chemotherapeutic agents in TNBC
Taxanes
Anthracyclines
Cyclophosphamide
Platinum agents
Fluorouracil
Ixabepilone
Surgery and radiotherapy
Targeted therapeutics for TNBC
Antiandrogen treatment
Histone deacetylase inhibitors and heat shock protein 90
Antiangiogenesis therapy
Estrogen receptor ER-ɑ36
MEK inhibitors
Cancer stem-cell population inhibitors
Antibody-drug conjugates (ADCs)
Role of immunotherapy in the treatment of TNBC
Immunotherapy for TNBC with adenosine pathway blockade
Advanced treatment options for TNBC
MiRNA and lnRNAs
siRNA
Summary
References
Chapter
4 - Conventional adjuvant chemotherapy in combination with surgery, radiotherapy, and other specific targets
Introduction
An overview of chemotherapy
Neoadjuvant chemotherapy
Neoadjuvant CT containing anthracyclines and taxanes
Neoadjuvant platinum agents in TNBC and BRCA mutation
Adjuvant chemotherapy
An abbreviated history of adjuvant systemic therapy
Adjuvant chemotherapy: First, second, and third generation regimens
Anthracyclines
Taxanes
The case for chemotherapy in TNBC
Principles for adjuvant and neoadjuvant CT
Standard chemotherapy regimens in the neoadjuvant and adjuvant settings
Platinum-based CT in TNBC
Poly ADP ribose polymerase (PARP) inhibitors in TNBC
Vascular endothelial growth factor (VEGF) inhibitors in TNBC
The case of BRCA-mutant TNBCs: PARP and platinum
Surgery in TNBC
The impact of TN status on surgical decision making
Chemotherapy before surgery vs after surgery
Radiotherapy in TNBC
Radiotherapy for TNBC after BCS
Radiotherapy after mastectomy in TNBC individuals
Radiosensitization
Chemotherapy in combination with radiotherapy (chemoradiotherapy) in TNBC
Chemotherapy combining specific target molecules in TNBC
EGFR
Androgen receptor (AR)
Estrogen receptor ER-α36
Mammalian target of rapamycin (mTOR)
Summary
References
Chapter
5 - Role of immune system in TNBC
Introduction
Cancer-immunity cycle
Immune system in cancer –a friend or FOE
Role of immune cells in cancer progression
Macrophages
Neutrophils
NK cells
Dendritic cells (DCs)
T cells
Myeloid-derived suppressor cells (MDSCs)
Cancer-associated fibroblasts (CAFs)
B cells
Immune system and TNBC
Immunological portrait of TNBC
TNBC cell
Tumor microenvironment
Immune checkpoints in TNBC
Tumor in filtering lymphocytes (TILs) in TNBC
Subpopulations of TILs in TNBC
CD8+
CD4+
Clinical significance of TILs in TNBC
Role of TILs in prognosis
Role of TILs as a predictive factor
Role of TILs as a biomarker of residual disease
PD-L1 – expression in TNBC
CTLA-4- expression in TNBC
PD-1
Newly emerging immune checkpoints
LAG-3 (lymphocyte activation gene-3)
B and T lymphocyte attenuator (BTLA)
PD-1 H
TIM/CEACAM1-L
Poliovirus receptor (PVR) - like proteins
IDO-1 (indole amine 2, 3- dioxygenase 1)
TNBC metastasis and recurrence
Summary
References
Chapter
6 - The interplay of immunotherapy, chemotherapy, and targeted therapy in tripple negative breast cancer (TNBC)
Introduction
An overview of immunotherapy in TNBC
Immunotherapy’s potential in TNBC: Variables to be considered
Choosing the proper immunotherapy and chemotherapy combination
Anthracyclines
Taxanes
Cyclophosphamide
Gemcitabine
Platinum salts
Immune checkpoint blockades in TNBC
Inhibiting the PD1/PDL1 pathway in TNBC
PD1/PD-L1 antibody monotherapy
PD1/PD-L1 Ab chemotherapy combination treatment
Inhibiting the CTLA4 molecule in TNBC
Humanized Abs against CTLA4
Combination treatments involving PD1/PD-L1
Dual application of ICIs (anti-CTLA-4 and anti-PD-1) in TNBC
PD1/PD-L1 Ab – targeted treatment combinations
PD1/PD-L1 Ab – vaccine treatment combinations
PD/PD-L1 Ab-NK cell combination treatment
Anti-PD-1/PD-L1 in combination with anti-MMP-14 antibodies for potential use
Adoptive cell therapy
Chimeric antigen receptors T-cell containing therapy
T cell receptors (TCRs) - engineered T cells
Cancer vaccines
CTA - vaccine target
Personalized peptide vaccination (PPV)
APC and DC-based tumor vaccination
Resistance to ICI
Moving immunotherapy to early TNBC
Efficacy of immunotherapy and future perspectives in TNBC
Synergistic impact of immunotherapy and CT
Antibody-drug conjugates (ADC)
Summary
References
Chapter
7 - Targeting biologically specific molecules in triple negative breast cancer (TNBC)
Introduction
An overview of targeted therapy
Signaling pathways to be targeted in treating TNBC
Notch signaling pathway
Hg signaling pathway
Wnt/β-catenin pathway
TGF-β signaling pathway
Inhibiting JAK2/STAT3 pathway
Pi3K/AKT/mTOR pathway
Overexpressed growth factors in TNBC
Inhibition of fibroblast growth factor receptor (FGFR)
Epidermal growth factor receptor (EGFR) targeted therapy
Vascular endothelial growth factor (VEGF) inhibitors in TNBC
Targeting the specific agents in the treatment of TNBC
Targeting Trop-2
PARP inhibitors targeting PARP
Angiogenesis inhibitors
Estrogen receptor ER-α36
AR inhibitors
Experimental targets for TNBC under study
AMPK (AMP-activated protein kinase)
Mouse double minute-2 homolog (MDM2)
Metadherin (MTDH)
Heat shock protein
Cell cycle regulating targets: Aurora kinase, CHK1, ATR, WEE1, and CDC25
Summary
References
Chapter
8 - Different drug delivery approaches in combinational therapy in TNBC
Introduction
Nanocarriers as targeted drug delivery systems
A multifunctional spherical nanocarrier: Liposomal nanoparticles
A cancer therapy miraculous ball: micelles
The siRNA delivering nanoparticles: Dendrimers
Polymeric nanoparticles
DNA nanostructures in treatment of cancer
Metal nanoparticles
A foldable graphene for cancer treatment: Carbon nanotubes (CNTs)
Ligands for targeted TNBC treatment
Nucleic acid-based ligands: Aptamers
Dual-functioning Y-shaped key: Antibodies
Peptides
VLPS (virus-like particles) as unique nanocarriers
Role of nanomedicine in breast cancer treatment: A transition from traditional to nanomedicine
Nanoparticles relying on the EPR effect for passive targeting of TNBC cells
TNBC treatment using folate receptor-targeted nanoparticles
TNBC therapy using CD44 receptor-targeted nanoparticles
Nanoparticles that target the receptor for advanced glycation end products (RAGE) for the treatment of TNBC
TNBC therapy using EGFR-targeted nanoparticles
Nanoparticles targeting the transferrin receptors for TNBC therapy
TNBC therapy using macrophage-targeted nanoparticles
TNBC therapy with high-density lipoprotein (HDL) receptor-targeted nanoparticles
TNBC therapy using extracellular matrix-targeted nanoparticles
Gene delivery
Photothermal therapy
Photodynamic therapy
Nanosoldiers to suppress TNBC metastasis
Nanosoldiers to combat brain metastases in TNBC
Nanosoldiers to combat lung metastases in TNBC
Stimulus responsive drug delivery
TNBC therapy with pH-responsive nanosoldiers
TNBC therapy using magnetic hyperthermia responsive nanosoldiers
Summary
References
Glossary
Abbreviations
Index
