Meet the editor

Dr. Ren Huan is Professor at the School of Medicine, Southern University of Science and Technology, China. She obtained a master's degree in Immunology from Harbin Medical University, China, and a PhD in Neuroscience from the University of Liverpool, UK. From 2006 to 2018, she served as a professor and head of the Department of Immunology at Harbin Medical University. As the principle investigator, Dr. Ren and her team have accom-

plished several research projects funded by the National Science Foundation of China. Their research focuses on the mechanisms and strategies of tumor microenvironmental factor-targeted immuno- and bio-therapies. Dr. Huan has published books and more than 70 peer-reviewed papers in academic journals including *Nuclear Acid Research*, *Neuro-oncology*, *Cell Death & Differentiation*, *Molecular Cancer Therapeutics, BMC Immunology*, and others.

Contents

**Section 1**

*by Huan Ren*

Malignancies

**Section 3**

**Section 2**

**Preface III**

Introduction - Tyrosine Kinases as Druggable Targets in Cancer **1**

**Chapter 1 3** Introductory Chapter: Tyrosine Kinases as Drug Targets in Cancer Treatment

Non-receptor Tyrosine Kinases in Cancer Development and Treatment **9**

**Chapter 2 11**

**Chapter 3 45**

Cancer Treatment by Tyrosine Kinase Inhibitors **71**

**Chapter 4 73**

**Chapter 5 91**

Non-receptor Tyrosine Kinases Role and Significance in Hematological

*by Carlota Recio, Haidée Aranda-Tavío, Miguel Guerra-Rodríguez, Mercedes de Mirecki-Garrido, Patricia Martín-Rodríguez, Borja Guerra* 

Noncoding RNAs as Predictive Biomarkers of Therapeutic Response

Cancer Management by Tyrosine Kinase Inhibitors: Efficacy, Limitation,

*by Venice Wing Tung Ho, Hor Yue Tan, Ning Wang and Yibin Feng*

*by Ana Azevedo, Susana Silva and José Rueff*

JAK, an Oncokinase in Hematological Cancer

to Tyrosine Kinase Inhibitors in Metastatic Cancer

*and Leandro Fernández-Pérez*

*by Julia Kovacova and Ondrej Slaby*

and Future Strategies

## Contents


Preface

Protein tyrosine kinases (PTKs) are a subclass of protein kinase and include receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). RTKs are high-affinity cell surface receptors for many growth factors, cytokines, and hormones, such as EGFR, PDGFR, IGFR, Eph, RET, and DDR. nRTKs are cytosolic enzymes including Src, Abl, ZAP70/Syk, and JAKs. PTKs function as an "on" or "off" switch in many cellular functions, including cell growth, differentiation, adhesion, migration, apoptosis, and so on. nRTKs especially are critical components in regulating hematological functions. PTK deregulation via genetic or epigenetic changes can contribute to the growth of cancer and other diseases, and therefore PTKs are particularly important today because of their implications in cancer treatment. Up to now, numerous tyrosine kinase inhibitors (TKIs) targeting various PTKs have been generated and proven to be effective anti-cancer agents. In this book, we review a few aspects of PTKs and cancer, considering efficacy, predictive markers to therapeutic response, limitations, and future directions in

As nRTKs play a key role in the development of human malignancies, hematological and otherwise, through their regulation of several vital cellular mechanisms, in their chapter, Ana Azevedo et al. summarize nRTKs of nine subfamilies, their structure, mechanisms of action, and physiopathology. They delineate the importance of JAK- STAT pathways regarding their genetic changes leading to aberrant activation, which is clinically significant mainly in Philadelphia chromosome-negative myeloproliferative neoplasms (PN-MPNs). Additionally, in a related chapter, Carlota Recio et al. discuss the complex signaling of JAK proteins in cancerous cells; various JAK aberrations implicated in myeloproliferative neoplasms, leukaemia, and lymphoma; and clinically available JAK TKIs in cancer therapy. A non-coding RNA (ncRNA) is a RNA molecule that is not translated into a protein that functions at epigenetic levels for DNA and RNA regulation. In their chapter, Ondrej Slaby and Julia Kovacova provide updated information on non-coding RNAs as predictive biomarkers of therapy response to TKIs in cancer. In the final chapter, Yibin Feng et al., presents an overall picture of TKI clinical use, and the considerations and

perspectives in overcoming the limitations in cancer treatment.

nation therapy as ongoing strategies.

In this book, we present the most up-to-date information on PTKs and TKI treatment for cancer. In this rapidly evolving field, overcoming therapeutic resistance is most challenging, and multi-targeting will direct next-generation TKIs and combi-

> **Huan Ren** Medical School,

Shenzhen, China

Southern University of Science and Technology,

TKI treatment in oncology.
