Preface

This book is intended primarily for researchers in translational oncology research, clinical oncology, and members of other professions such as medical researchers and radiography. It focuses on translational research in oncology, which has led to improvements in molecular diagnosis, tumor heterogeneity, and newer systematic therapies. This has brought challenges to the clinic in terms of patient education, toxicity management, workflow, and prognostication for palliative care.

Normally, the immune system is responsible for monitoring and getting rid of molecules or cells outside the body that can be potentially malignant. The immune system works to eliminate malignant cells; however, for reasons not well established yet, at some point, the immune system fails, and the malignant cells survive and establish. Importantly, IL-10 can exert the antitumor effect by mechanisms such as the activation of natural killer cells (NK), lymphocytes T, macrophages, and nitric oxide. The authors have presented the importance of IL 10 in cancer diagnosis and prognosis.

The book includes a chapter on ion channels and transporters (ICTs), emerging as potential cancer biomarkers. ICTs are aberrantly expressed in several types of human cancers, and exert a relevant role in mediating interactions between tumor cells and the tumor microenvironment. Such interactions drive different functions that in turn regulate neoplastic progressions, such as cell proliferation and survival, cell invasiveness, and pro-angiogenetic programs. Hence targeting ion channels and transporters for cancer diagnosis with antibodies becomes the need for cancer research to throw light on the discovery of many novel methods.

The book highlights that the epigenetic enzyme activity has been altered in cancer and contributes to the genomic instability in cancer cells. It is crucial to develop targeted therapeutic treatments to restore their normal function. Targeted therapy involves the use of drugs that target a specific biological molecule/pathway or drug treatment that requires genome profiling of an individual before it can be administered. Further it brought about the current update on epigenetics in the cancer treatment paradigm.

An effort has been made to give a synopsis of each different aspect of translational research in clinical oncology at the present time, which we hope will be of interest and benefit to all future researchers in clinical oncology.

**II**

**Chapter 9 143**

**Chapter 10 155**

**Chapter 11 173**

**Chapter 12 187**

Implications of Radiosensitizer and Radioprotector Factors in Refining

*by Camil Ciprian Mirestean, Călin Gheorghe Buzea, Roxana Irina Iancu* 

NQO1-Bioactivatable Therapeutics as Radiosensitizers for Cancer

*Jayne Silver, I-Ju Yeh, S. Louise Pay, Xiaolin Su, Kristen A. Russ,* 

Acquisition and Management of Data for Translational Science

*by Thomas J. FitzGerald, Maryann Bishop-Jodoin, Fran Laurie, Richard Hanusik, Matthew Iandoli, Kathryn Karolczuk, Sandra Kessel, Fred Prior, Joel Saltz, Ashish Sharma, Michael Knopp, Mark Rosen, Ying Xiao, David Followill, Jeff Michalski, Ameer Elaimy, James Shen,* 

the Dose-Volume Constraints and Radiobiological Models

*Peter Lee, Maria Giulia Cicchetti and Janaki Moni*

*David A. Boothman and Erik A. Bey*

Brachytherapy in Endometrial Cancer

*by Mehmet Sait Bakir*

*and Dragoș Petru Teodor Iancu*

in Oncology

*by Naveen Singh, Edward A. Motea, Xiumei Huang, Colton L. Starcher,* 

Treatment

**Sivapatham Sundaresan** SRM Institute of Science and Technology, India

> **Yeunhwa Gu** Junshin Gakuen University, Japan

**1**

**Chapter 1**

**Abstract**

Discovery of Small Molecule

Methyltransferases in Cancer

*Aishat A. Motolani, Mengyao Sun, Matthew Martin,* 

Cancer is the second leading cause of mortality in the United States. There are several therapeutic regimens employed to mitigate the mortality rate of cancer. This includes the use of chemotherapy, radiation, immunotherapy, and precision medicine/targeted therapy. Targeted therapy involves the use of drugs that target a specific pathway or biomolecule compromised in cancer for cancer treatment. Aberrant expression of epigenetic enzymes has been well documented for their contribution in driving tumorigenesis and other cancer hallmarks. Hence, there is an urgent need for novel drug discovery and development in epigenetics to help combat various cancer morbidities. Herein, we review the roles and consequences of dysregulated function of several epigenetic enzymes, with a focus on histone methyltransferases (HMTs). Additionally, we discussed the current efforts made in the development of small molecule inhibitors for a few representative HMTs implicated in different cancers. Furthermore, the common screening assays used in discovering potent small molecule inhibitors were also detailed in this chapter. Overall, this book chapter highlights the significance of targeting HMTs in different cancers and the clinical application potentials/limitations faced by the developed or emerging small molecule inhibitors of HMTs for the purpose of cancer therapy.

**Keywords:** cancer, drug discovery, epigenetics, histone methyltransferases,

Since the conception of the term "epigenetic landscape" by Conrad Waddington in 1940, the field of epigenetics has rapidly evolved with technological advances. In the study of embryonic development, it was observed that a single gene has the ability to produce different phenotypes, so epigenetics was used to describe the mechanisms through which that happens [1]. Today, epigenetics is defined as the study of changes in organisms caused by modification of gene expression through addition and removal of chemical groups to nucleotides and proteins rather than the alteration of the genetic code itself [2]. The human genome contains approximately 3 billion bases of nucleotides and they are compacted into chromosomes in the nucleus via histone proteins. About 146 base pairs of nucleotides are wound around core histone octamers and are sealed with the linker histone (H1) to form a nucleosome.

Inhibitors for Histone

*Steven Sun and Tao Lu*

small molecule inhibitors

**1. Introduction**
