Preface

Every year, almost 10 million people succumb to death around the world due to one or the other type of cancers. Hundreds of laboratories with thousands of scientists are trying to understand the ever-enigmatic biology of cancer cells, which is the basis for developing new therapies for cancer. Discovery of antifolates aminopterin in 1947 and methotrexate (aka amethopterin) in 1948 as potential anticancer agents by Drs. Yellapragada Subbarow and Sydney Farber not only initiated the era of chemotherapy but the discovery of these synthetic agents also infused the hope that cancers can be treated with synthetic chemicals. In the past more than seven decades, we have witnessed the journey of cancer therapy that started from nonspecific chemotherapy (e.g. antifolates) to targeted biologic agents (e.g. monoclonal antibodies) and now the era of personalized treatment (e.g. CART cells) and immunotherapy. However, deeper understanding of the signal transduction within the cancer cells, and between cancer cells and their surrounding tumor microenvironment has remained central to the development of therapies.

In the present volume 1 titled ‘Advances in Cancer Signal Transduction and Therapy’ of the book series ‘Recent advances in signal transduction research and therapy’, we attempted to review recent advances in select cancer signal transduction pathways that have been targeted or could be potential targets for developing therapeutics for cancers. It would be too exhaustive to cover all the signaling pathways in all cancer types and we do not intend to do so, and due to the very rapidly progressing research on cancer signaling and therapy, we have no doubt that new discoveries will have been made by the time this book is published.

In the first chapter of this book, Fultang et al., dive into the role of Wingless and Int-1 (Wnt) signaling in breast cancer oncogenesis. Moreover, the authors also review the current inhibitors of Wnt signaling that are under investigation. The C-X-C chemokine receptor type 4 (CXCR4) signaling is critical in hematological malignancies, while its role in breast cancer is still unraveling. In the second chapter Raman et al., explain the intersection of CXCR4 signaling with other signaling pathways such as Phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), cellular Src (c-Src) and Janus kinases-signal transducer and activator of transcription proteins (JAK-STAT) in breast cancer progression and metastasis. A key role of epidermal growth factor receptor (EGFR) signaling in cell proliferation and survival in various cancers is now well known. Here in the third chapter, Meena et al., discuss the role of EGFR in colon cancer and its prospective importance as a target for colon cancer therapy. The critical role of PI3K/AKT (protein kinase B)/mammalian target of rapamycin (mTOR) signaling pathway in various cancers has attracted cancer researchers for a long time. Yadav and Mishra elucidate the PI3K/AKT/mTOR signaling in hepatocellular carcinoma and review the various drugs under investigations that target this pathway in the fourth chapter. The MAPK pathway is one of the key survival pathways that have been targeted to develop cancer therapeutics. In chapter 5, Prasad and Srivastava review MAPK signaling in pancreatic cancer and therapeutic agents under investigation. Aberrant regulation and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been implicated in several cancers, inflammatory and autoimmune disorders, and erroneous immune system development. In chapter 6, Arora et al., summarize the role of NF-κB activation specifically in multiple myeloma and various strategies developed for its potential pharmacological intervention to abrogate the process of cancer cell proliferation. Recently, small-molecule inhibitors of Bruton’s tyrosine kinase (BTK) such as ibrutinib have shown an impressive anti-tumor activity in clinical studies in patients with various B cell malignancies. BTK is crucial in B lymphocyte development, differentiation and oncogenic signaling. In chapter 7, Gowda et al., elucidate the role of BTK in B cell malignancies and highlight the current progress in the discovery of small molecule BTK inhibitors. Finally, in the last chapter of this book, Pathania et al., discuss the interconnection between exosomes, tumor microenvironment and cMyc transcription factor, and therapeutic strategies to break that nexus.

We sincerely hope that you will enjoy diving into this book.