Etiological Insights into TNBC and their Related Catastrophic Risks
Page: 1-25 (25)
Author: Haritha H. Nair and Ruby John Anto*
DOI: 10.2174/9789815079784123010004
PDF Price: $15
Abstract
Triple-negative breast cancer is the most aggressive form of breast cancer
that lacks expression of estrogen, progesterone, and human epidermal growth factor
receptor 2. TNBC is characterized by poor clinic-pathological attributes, prognostic
markers, unavailability of efficient therapeutic approaches, and higher chances of
disease relapse along with metastasis to distant sites. Dysregulated epigenetic and
transcriptional profiling was involved in cancer progression including histone
modification, altered miRNA, DNA methylation, and long non-coding RNA signatures.
This chapter will provide an insight into the molecular biology of TNBC including
gene expression patterns and their subtypes. TNBC molecular spectrum was
extensively studied to depict the distant metastasis-free survival and overall survival
rate in affected individuals. Prevalence and epidemiology trends of TNBC patients
across the globe were also studied to determine the impact of genetic predisposition
and socioeconomic factors behind its aggressive behavior.
A Clinical Cognizance of Molecular and Pathological Diagnostic Approach of TNBC
Page: 26-46 (21)
Author: Acharya Balkrishna, Usman Umar Zango, Saima Kauser Nasir and Vedpriya Arya*
DOI: 10.2174/9789815079784123010005
PDF Price: $15
Abstract
Genetic, transcriptional, and clinical heterogeneity of disease has remained
to be a prominent obstacle to the development of a targeted therapeutic approach
against TNBC. So far, based on tumor size, lymph node status, and histologic features
TNBC subtypes were stratified. Insights into inter and intratumoral heterogeneity of
TNBC were gained by next-generation sequencing, genomic, transcriptomic,
proteomic, and clinicopathological characterization. To depict tumor response to
neoadjuvant chemotherapy, radiological characterization may also a play significant
role. Biomarkers for subtyping TNBC were highly needed to depict the survival
outcome. This chapter discussed the available and possible molecular and pathological
diagnostic approaches to TNBC. Furthermore, the integration of morphological and
genomic data may emerge as a promising approach for the identification of new
therapeutic and prognostic markers to predict the likely outcome of the disease. This
chapter aims to highlight the molecular and pathological diagnostic approaches to
depict both metastatic and non-metastatic TNBC.
Molecular Sub-Typing and Exploration of Key Signalling Pathways Involved in Complicating the Disease
Page: 47-72 (26)
Author: Nikhil Ponnoor Anto, Amitha Muraleedharan and Rashmi Mittal*
DOI: 10.2174/9789815079784123010006
PDF Price: $15
Abstract
Triple-negative breast cancer is characterized by distinct molecular profiles,
unique metastatic patterns, aggressive behavior, lacks the targeted therapeutic
approach, and caused significant mortality worldwide. The molecular complexity of
angiogenesis, autophagy, apoptosis, and metastasis process in TNBC has fostered
research efforts to unleash the molecular, pathological, and genetic drivers of their
lethal cascade. This complex disease entity involves PI3k/Akt/mTOR, NF-kB, ERRs,
and miRNA trafficking which has further worsened the clinical outcome. Due to their
heterogeneous nature, none of the drugs were able to completely target the TNBC
tumor spectrum. This chapter highlights the classification of TNBC on the basis of
aberrated copy number, histology, proteomic, and mutational profiles to understand the
aetiology of the disease. The identification of therapeutic vulnerabilities was also
carried out by gaining insights into the above-mentioned signalling pathways and their
role in further complicating the disease.
Pre-Clinical and Clinical Evidence of Recent Therapeutic Trends and Spotting Possibility of Cure in Near Future
Page: 73-98 (26)
Author: Amitha Muraleedharan, Sagar Kumar and Rashmi Mittal*
DOI: 10.2174/9789815079784123010007
PDF Price: $15
Abstract
Substantial cohort studies, pre-clinical, clinical trials, and in-depth genomic
and proteomic analysis underlie that several molecular alterations exist in TNBC that
may be favorable or detrimental to cancer progression. Molecular heterogeneity in
TNBC has shortened the disease-free survival rate in response to adjuvant and
neoadjuvant therapies. To determine possible vulnerabilities in TNBC, several drugs
were under investigation. This chapter highlighted the current paradigm of the
therapeutic approach including surgery, radiotherapy, and chemotherapy. In this
review, we also highlighted the clinical trials involved in the management of TNBC by
targeting angiogenesis, apoptosis, androgen receptors, cell cycle, and pro-survival
signalling pathways. To overcome the constraints associated with the mono-therapeutic
approach, pre-clinical and clinical studies of combinational therapy have also been
discussed to improve OS, DFS, and DMFS in TNBC patients.
Evaluating Fate of Emerging Resistance Hitting the Brakes on Conventional Treatment Approach
Page: 99-122 (24)
Author: Nikhil Ponnoor Anto and Rashmi Mittal*
DOI: 10.2174/9789815079784123010008
PDF Price: $15
Abstract
The tumor microenvironment of TNBC cells was associated with the induction of angiogenesis, proliferation, apoptosis inhibition, immune suppression, and drug resistance. TME creates a niche for the survival and interaction of cancer cells with surrounding cells. TME promoted epithelial to mesenchymal transition, stemness, and chemoresistance and ensured the escape of TNBC cells from the chemotherapeutic and immunological responses. This chapter highlighted the role of cancer stem cells, hypoxia, lysosomal biomass, tumor-associated macrophages, PTEN, PI3K/Akt/mTOR pathway, and ABC transporters in inducing resistance against standard therapeutic regimens. The possible role of miRNA, transcriptional signatures, and tumorinfiltrating lymphocytes as a predictor of chemoresistance was also depicted. The impact of drug repurposing and combinational therapeutic approach to overcome the obstacle of chemoresistance have been underlined in this chapter for the treatment of TNBC.
Herbal Medicine: Prejudice to Realm of Reality Against TNBC
Page: 123-144 (22)
Author: Balachandran S. Vinod and Ruby John Anto*
DOI: 10.2174/9789815079784123010009
PDF Price: $15
Abstract
In triple-negative breast cancers, there exist tumor-specific vulnerabilities
that can be targeted to avoid compensatory adaptation of cancer cells in response to
standard pharmaceutical therapies. Natural moieties are well-known to possess a
multitude of medicinal properties and deserve attention for TNBC prevention and
therapy. To overcome drug resistance and efficacy issues, the exploration of natural
moieties as targeting agents may emerge as dynamic, promising, and new therapeutic
strategies to benefit TNBC patients. This chapter summarizes the role of
polysaccharides, flavonoids, phenols, saponins, and taxanes in targeting TNBC. The
potent role of herbal medicine in targeting molecular signalling pathways with special
emphasis on their ability to target uncontrolled proliferation, metastasis, angiogenesis,
and autophagy has also been discussed. Furthermore, the ability of herbal medicine in
inhibiting PI3K/Akt/mTOR, STAT3, and Wnt/β-Catenin has also been explored.
Combinational therapy comprising chemotherapeutic drugs and active plant
constituents was also explored to overcome the complications of TNBC.
Unveiling the Potency of Phyto-Constituents to Target TNBC: Mechanism to Therapeutics
Page: 145-160 (16)
Author: Sreekumar Usha Devi Aiswarya and Smitha V. Bava*
DOI: 10.2174/9789815079784123010010
PDF Price: $15
Abstract
The development of an effective therapeutic approach against TNBC is a
formidable challenge at present. Efficacy and drug resistance issues in response to
adjuvant and neoadjuvant chemotherapy have prompted the development of new
therapeutic regimens. In this concern, the scientific community has started exploring
natural sources including medicinal plants exhibiting anti-cancer activity for their
potent inhibitory potential against TNBC. The comprehensive analysis underlying the
molecular mechanism of action of these natural bio-compounds provided substantial
evidence to subject a few of these for clinical application. This chapter highlighted the
momentous phytoconstituents as a genetic or epigenetic modulator by inducing
demethylation and histone deacetylation in TNBC. Bioactive phytoconstituents
including berberine, luteolin, cantharidin, saikosaponin D, wogonoside, and others
targeted cell proliferation, metastasis, angiogenesis, autophagy, and induced apoptosis
in TNBC. Furthermore, combinational therapy comprising phytoconstituents and
chemotherapeutic drugs was explored to improve the clinical outcome of the disease.
Additionally, drug ability parameters including bioavailability and bio-absorption of
these phytoconstituents were also discussed.
Phyto-nanotechnology: Enhancing Plant Based Chemical Constituent Mediated Anticancer Therapies
Page: 161-181 (21)
Author: Usman Umar Zango, Aminu Abubakar, Rohit Saxena and Vedpriya Arya*
DOI: 10.2174/9789815079784123010011
PDF Price: $15
Abstract
95% of anti-cancer agents were associated with the worst pharmaceutical and pharmacokinetic properties including poor targeted cellular uptake, shorter halflife, toxicity, and many more. In this regard, nanotechnology including nanomedicines, nano-carriers, and nanomaterials may emerge as a beneficial tool to facilitate an efficient delivery of therapeutic regimens by adapting active or passive targeting mechanisms. The nanotechnology-based delivery system of phytoconstituents can efficiently battle against recalcitrant TNBC. This chapter highlighted the nanotechnology-based therapeutic approach including smart nanoparticles, cell membrane-coated nanoparticles, and immunological cell-based nano-systems for the treatment of TNBC. Furthermore, the role of nano-soldiers in improving bioavailability and targeted drug delivery was highlighted. Nano conjugates of curcumin, anacardic acid, EGCG, betulinic acid, gambogic acid, and resveratrol were also evaluated to enhance the pharmacokinetic profile, distribution, and the release rate of respective compounds and ultimately their ability to target TNBC.
Novel Implications of Prognostic Markers to Monitor the Disease: An Overview
Page: 182-197 (16)
Author: Rohit Saxena, Ankit Gupta, Vikrant Singh, Vipin Kumar Singh, Sagar Kumar and Rashmi Mittal*
DOI: 10.2174/9789815079784123010012
PDF Price: $15
Abstract
Apart from the absence of targeted therapies, poor prognosis in TNBC has
affected the clinical outcome of the disease and has led to cause high mortality rate
amongst diseased individuals. The discovery of potential biomarkers to determine the
prognostic and predictive value may play a vital role in the development of an effective
therapeutic approach and may improve the OS, DFS, and DMFS. This chapter
highlighted the role of histological subtyping, lymph node status, lymphovascular
invasion, miRNA, Ki-67, TILs, and BRCAness as prognostic markers of diseases.
Nevertheless, patient selection and choice of treatment strategy will greatly impact the
clinical efficacy of these prognostic markers but will remain to be a matter of further
exploration.
Stumbling Blocks in Reinvigorating the Health of Diseased Individuals Through Herbal Medicine
Page: 198-207 (10)
Author: Acharya Balkrishna, Rashmi Mittal and Vedpriya Arya*
DOI: 10.2174/9789815079784123010013
PDF Price: $15
Abstract
Natural products exhibited a profound effect as a template or direct
treatment strategy against TNBC. Implementation of natural products as a
chemotherapeutic or chemo-preventive strategy faces diverse problems and challenges.
Several constraints including selection, identification, and screening of bioactive
components furthermore, preclinical and clinical evaluation, and approval from
regulatory bodies are other hurdles to the application of phytochemicals in targeting
TNBC. Although the natural metabolites possessed the substantial potential to target
the disease along with reinvigorating the health of affected individuals. This chapter
has highlighted the perspectives and controversies associated with herbal medicines
such as consumer preferences, bio-pharmaceutics consideration, HM-HM & HM-CM
interactions, and drug regulations, and discussed the need to introduce natural moieties
as an alternative therapeutic approach against TNBC.
Introduction
Triple negative breast cancers (TNBC) are a biologically aggressive form of breast cancer and constitute approximately 10-15% of all breast cancer patients. Distant metastasis, lack of clinically targeted therapies and prognostic markers, makes the disease difficult to treat. Till now not much work has been carried out on this deadly disease. This book provides an overview of TNBC etiology, its treatment strategies and prognostic markers to identify the outcome of standard therapies. Signalling pathways namely cell proliferation, angiogenesis, invasion and metastasis, apoptosis, autophagy and others involved in complicating the disease have been described in the chapters to convey an understanding about the disease mechanisms. All the possible drugs either in pre-clinical or clinical stages have also been mentioned with data that depicts their efficiency in targeting altered genes. The book also introduces the reader to herbal medicine exhibiting high potency to target TNBC, their synthetic analogs used during chemotherapy and their ability to fight against chemoresistance. The concept of phytonanotechnology has also been discussed. The book helps create awareness among a broad range of readers about TNBC. It points to prioritizing the upgradation of health care facilities and re-designing future treatment strategies to provide maximum benefit to breast cancer patients.