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 TKI treatment in oncology.

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.

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 combination therapy as ongoing strategies.

> **Huan Ren** Medical School, Southern University of Science and Technology, Shenzhen, China

**1**

Section 1

Introduction - Tyrosine

Kinases as Druggable

Targets in Cancer

### Section 1
