**Meet the editor**

Dr. Ajay Gupta MD, is a Senior Consultant in Medical Oncology at Max Cancer Center in New Delhi. He received the 2008 American Society of Clinical Oncology (ASCO) Foundation Brigid Leventhal Award for Pediatric Oncology (for the best work in pediatric cancer research) for his work entitled 'Randomized control trial comparing efficacy of oral amoxicillin-clavulanate and

ofloxacin with intravenous ceftriaxone and amikacin as outpatient therapy in pediatric low-risk febrile neutropenia'. His professional interests include hematology and bone marrow transplants. He received his medical oncology fellowship from the All India Institute of Medical Sciences in New Delhi. Dr Gupta also trained in cardiology and internal medicine and has received the Certificate of Completion of Specialist Training (CCST) from the Specialist Training Authority of Medical Royal Colleges in General Internal Medicine in the UK.

Contents

**Preface IX** 

**Part 1 Multiple Myeloma:** 

Chapter 1 **Proteasome Inhibitors in** 

**Disease Biology and It's Therapeutic Applications 1** 

**the Treatment of Multiple Myeloma 3**  Lisa J. Crawford and Alexandra E. Irvine

Karthick Raja Muthu Raja and Roman Hajek

**Factor-α and Its Combination with Native Human Leukocyte Interferon-α on P3-X63-Ag8.653** 

Je-Jung Lee, Youn-Kyung Lee and Thanh-Nhan Nguyen-Pham

Radhamani Kannaiyan, Rohit Surana, Eun Myoung Shin, Lalitha Ramachandran, Gautam Sethi and Alan Prem Kumar

Chapter 2 **Regulatory Cells and Multiple Myeloma 33** 

Chapter 3 **Effects of Recombinant Human Tumor Necrosis** 

**Mouse Myeloma Cell Growth 61**  Andrej Plesničar, Gaj Vidmar,

Chapter 4 **Cellular Immunotherapy Using Dendritic** 

Borut Štabuc and Blanka Kores Plesničar

**Cells Against Multiple Myeloma 75** 

Chapter 5 **Targeted Inhibition of Multiple Proinflammatory Signalling Pathways for the Prevention and Treatment of Multiple Myeloma 93** 

Chapter 6 **The SUMOylation Pathway as a Potential Therapeutic** 

Chapter 7 **Therapeutic Approaches for Targeting Hypoxia-Inducible** 

**Target in Multiple Myeloma 129** 

**Factor in Multiple Myeloma 137** 

James J. Driscoll

Keita Kirito

### Contents

#### **Preface XI**


X Contents



## Preface

Multiple myeloma is a malignant disorder characterized by the proliferation of plasma cells. It accounts for 10% of hematological cancers and 1% of all cancers. The disease is uniformly fatal with a median survival of approximately three years with conventional chemotherapy, although the outlook has improved with the integration of newer therapies including high-dose therapy followed by autologous stem cell transplantation.

Much insight has been gained into the molecular pathways that lead to myeloma and indeed much more remains to be done. The understanding of these pathways is closely linked to their therapeutic implications and is stressed upon in the initial chapters.

The role of multiple pro-inflammatory pathways, hypoxia inducing factor, tumor necrosis factor, proteasomes , sumoylation pathways and their therapeutic importance is examined as is the role of experimental therapies like dendritic cell therapy.

Recently, the introduction of newer agents such as bortezomib, lenalidomide, thalidomide, liposomal doxorubicin, etc. has led to a flurry of trials aimed at testing various combinations in order to improve survival. Higher response rates observed with these agents have led to their integration into induction therapies. It has raised questions in terms of redefining the inclusion criteria/timing and expected benefits of stem cell transplantation.

The role of various new therapies vis a vis transplantation has also been examined. Recent advances in the management of plasmacytomas , renal dysfunction, dentistry as well as mobilization of stem cells in the context of myeloma have also found exclusive mention. These areas are clinically very relevant and are often neglected in text books on multiple myeloma. A complete book on the topic would be too exhaustive: as such, since brevity is the soul of wit our attempt has been to present before the reader a comprehensive yet brief text on this important subject.

> **Ajay Gupta**  MD, DM, CCST (UK), Senior Consultant, Medical Oncology, Max Cancer Centre, Saket, New Delhi, India

**Part 1** 

**Multiple Myeloma: Disease Biology** 

**and It's Therapeutic Applications** 
