Metastatic Diseases

Novel Approaches in Diagnosis and Therapeutic Management

Sandeep Arora, Tapan Behl, Sukhbir Singh, Neelam Sharma, Saurabh Gupta

• Publisher: Apple Academic Press
• Year: 2021
• eBook ISBN:
  9781000064933
• Topic: Medicina
• Subtopic: Oncología

This insightful volume opens new horizons for exploring modern therapeutic entities and emerging targets for combating the deadly disease of cancer. The authors provide a review of cancer along with descriptions of its molecular level mechanisms and emphasize the role of promising new therapies, including herbal therapies, that can be utilized for the treatment of metastatic diseases. The chapters look at specific approaches that have been researched and developed and that have almost reached the standardization stage, such as intracellular mechanisms, particularly phosphoprotein-enriched astrocytes and transthyretin proteins; CXCR4; autophagy-inhibiting drugs; spatiotemporal genetic analysis; tyrosine kinase inhibitors; and more. Also considered are advances in diagnostic systems like intra vital microscopy and molecular imaging.

CHAPTER 1

A Review on Cancer: From Clinical Perspective to Chemotherapy

SANDEEP ARORA and POOJA SHARMA

Chitkara College of Pharmacy, Chitkara University, Punjab, India

ABSTRACT

The primary trait of cancer is the unregulated growth and proliferation of abnormal cells. The normal physiological mechanism of the cells is not carried out with cancer cells, and they’re not responsive to average cell growth, proliferation, and survival process sequences. The number of individuals diagnosed with cancer was around 1.4 million in 2007. Therefore, healthcare practitioners play an integral role in the diagnosis and treatment of cancer. To control drug-induced toxicities, this becomes necessary for a cancer patient to understand pharmacology and pharmacotherapy of chemotherapeutic agents. Perceptive and skilled physicians contribute to public treatment in the oncology unit. Carcinogenesis is a multistage mechanism that is genetically regulated. Owing to mutated cells that are developed with the association of carcinogens to normal cells, these mutated cells behave differently to their environment; excessive production of tumor tissues produces characteristics morphological and physiological changes in the initial phase of induction. This chapter describes cancer from the scientific point of view of suggested possible therapies.

1.1 INTRODUCTION

Unrestricted growth and spread of abnormal cells are the distinguishing features of cancer. Being unresponsive to normal cell growth, proliferation, and survival, cells’ normal physiological function is not performed by the cancer cells. These cells can develop new tumors at a distant place by traveling through blood or lymph (metastasis); they also have a property to occupy adjacent normal tissue and separate from the primary tumor (metastasize). Their continuous growth and survival are promoted by their uncontrolled growth and their potential to prompt the formation of a blood vessel (Alldredge et al., 2012).

In 2007, the number of people diagnosed with cancer was about 1.4 million. It is essential to know anticancer drug pharmacology and pharmacotherapy in a cancer patient to manage drug-induced toxicities. In the oncology department, knowledgeable and trained health care professionals contribute extensively to patient care (DiPiro et al., 2017).

1.2 ETIOPATHOGEIVESIS

1.2.1 STEPS INVOLVED IN CARCINOGENESIS

Carcinogenesis is a genetically controlled multistage process. In the initial step of initiation, uncontrolled growth of neoplastic cells occurs due to the mutated cells which are formed with the interaction of carcinogens to normal cells, and these mutated cells respond differently to its environment. This is then followed by promotion, i.e., the second phase, in which cell alteration and mutated cell growth are observed over normal cells, induced further by carcinogens. The only difference between the two is that the promotion phase is reversible, whereas the initiation phase is irreversible. It may also be seen as the pointer to future chemoprevention strategies, including lifestyle and diet changes. Neoplastic growth marks the last stage of carcinogenesis, termed as progression; it is characterized by increased cell proliferation due to further genetic alteration. This phase includes tumor invasion into local tissues and metastases development (Calvo et al., 2005; Compagni and Christofori, 2000; Weston and Harris, 2003; Cotran et al., 1999).

1.2.2 CARCINOGENS

Chemical, physical, and biological agents constitute the three significant carcinogens (Weston and Harris, 2003). Chemical agents are discussed in Table 1.1 and are the associated cause of cancer. Also, ionization radiations and ultraviolet rays make up a part of the physical agents. These radiations cause the free radical formation known to damage the DNA (deoxyribonucleic acids) and result in mutations. Biological agents comprising of viruses may also become a cause for cancer; for example, the Burkitt’s lymphoma is caused by the Epstein-Barr virus, and cervical cancer is caused due to the infection of human papillomavirus, age, gender, diet, growth factors, and chronic irritation from the other promoters of carcinogens (Weston and Harris, 2003).

TABLE 1.1 Cancer causing Drugs and Hormones in humans

Drug or Hormone	Cancer Caused
Alkylating agents (e.g., chlorambucil, mechlorethamine, melphalan, and nitrosoureas)	Leukemia
Anabolic steroids	Liver
Analgesics containing phenacetin	Renal, Urinary bladder
Anthracyclines (e.g., doxorubicin)	Leukemia
Antiestrogens (tamoxifen)	Endometrium
Coal tars (topical)	Skin
Estrogens:
Nonsteroidal (diethylstilbestrol)	Vagina/cervix, endometrium, breast
Steroidal (estrogen replacement therapy, oral contraceptives)	Endometrium, breast, liver
Immunosuppressive drugs (cyclosporine, azathioprine)	Lymphoma, skin
Source: Compagni and Christofori (2000).

1.2.3 GENES ENTAILED IN CARCINOGENESIS

Oncogenes and tumor suppressor genes are the genes associated with the process of carcinogenesis.

1.2.3.1 ONCOGENES

Oncogenes originate from proto-oncogenes or normal genes and play a significant role in carcinogenesis. All normal cells have proto-oncogenes, which monitor cellular function (cell cycle). Exposure to any carcinogenic agents causes an alteration in the genome of these proto-oncogenes via chromosomal rearrangement, point mutation, or gene amplification that, in turn, triggers the oncogenes. There is an increase in the probability of neoplastic transformation due to impaired cell growth, which results in a distinct growth advantage to the cell. This is all due to the oncogene’s activation that produces an abundance of the abnormal gene product. HER (human epidermal growth factor receptor) is an example of oncogenes. Epidermal growth factor receptor or ErbB-1, HER-3, HER-2, and HER-4 are the four members present in this family having receptor tyrosine kinases (RTKs). In several cancers, proliferation, metastasis, angiogenesis, and cell survival happen once these receptors get activated, causing the acquiring of specialized features and rapid multiplication of cells through downstream signaling pathways and...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• About the Editor
• About the Co-Editors
• Table of Contents
• Contributors
• Abbreviations
• Preface
• 1. A Review on Cancer: From Clinical Perspective to Chemotherapy
• 2. Phosphoprotein-Enriched Astrocytes as Potential Anticancer Agents
• 3. Autophagy-Modulating Drugs as Complements to Cancer Chemotherapy
• 4. Transthyretin Protein in Renowned Metastatic and Other Conditions
• 5. Role of CXCR4 Receptor Protein in Cancer Development and Therapies
• 6. C3D Complement System in Immunotherapy-Based Cancer Treatment
• 7. BH3 Mimetics
• 8. Spherical Nucleic Acid Platform-Based Drug Delivery for Brain Cancer and Improved Blood-Brain Barrier Crossing for Alzheimer’s and Other Diseases
• 9. Intra-Vital Microscopy: A New Amelioration in Cancer Immunotherapy Monitoring
• 10. Molecular Imaging: A New Advancement in Cancer Immunotherapy Monitoring
• 11. Spatiotemporal Genetic Analysis (SAGA) Technique for Cancer Cell Biology Studies
• 12. Plant-Derived Anti-Malarial Compounds and Their Derivatives as Anticancer Agents: Future Perspectives
• 13. Epigenetic Control of the Immune System and its Applications in Metastatic Diseases
• 14. Immune Checkpoint Inhibitors
• 15. Tyrosine Kinase Inhibitors in Lymphocytic Leukemia
• 16. Cyclooxygenase-1 (COX-1) Inhibitors in the Management of Neoplastic Disorders
• 17. Microfluidic Devices in Capturing Circulating Metastatic Cancer Cell Clusters
• Index