Pancreatic cancer is a highly lethal gastrointestinal disease that is becoming one of the leading causes of cancer mortality worldwide. Despite advances in surgery, radiation therapy, immuno-oncology, and therapeutics, the 5-year survival rate for pancreatic cancer patients remains around 12%. The poor prognosis is mainly due to late diagnosis, as pancreatic cancer patients commonly don’t exhibit symptoms until an advanced stage that is beyond surgical resection. Currently, the main treatments for patients with advanced pancreatic cancer are chemotherapy, radiotherapy, and most recent clinical trials incorporate immunotherapy.

​This book presents drug repurposing strategies to combat infectious diseases and cancer. It discusses key experimental and in silico approaches for modern drug repositioning, including signature matching, molecular docking, genome-wide associated studies, and network-based approaches aided by artificial intelligence. Further, the book presents various computational and experimental strategies for better understanding disease mechanisms and identify repurposed drug candidates for personalized pharmacotherapy. It also explores the databases for drug repositioning, summarizes the approaches taken for drug repositioning, and highlights and compares their characteristics and challenges. Towards the end, the book discusses challenges and limitations encountered in computational drug repositioning.

This represents the third volume in a series on cancer markers pub lished by the Humana Press. The first volume, published in 1980, stressed the relationship of development and cancer as reflected in the production of markers by cancer that are also produced by normal cells during fetal development. The concept that cancer represents a problem of differentiation was introduced by Barry Pierce in describing differenti ation of teratocarcinomas. Highlighted were lymphocyte markers, alphafetoprotein, carcinoembryonic antigen, ectopic hormones, enzymes and isozymes, pregnancy proteins, and fibronectin. The second volume, published in 1982 and coedited with Britta Wahren, focused on the diagnostic use of oncological markers in human cancers, which were systematically treated on an organ by organ basis. At that time, the application of monoclonal antibodies to the identification of cancer markers was still in a very preliminary stage. A general introduc tion to monoclonal antibodies to human tumor antigens was given there by William Raschke, and other authors included coverage of those mark ers then detectable by monoclonal antibodies in their chapters.

This book systematically reviews the most important findings on cancer immune checkpoints, sharing essential insights into this rapidly evolving yet largely unexplored research topic. The past decade has seen major advances in cancer immune checkpoint therapy, which has demonstrated impressive clinical benefits. The family of checkpoints for mediating cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, and many others. Despite these strides, most patients do not show lasting remission, and some cancers have been completely resistant to the therapy. The potentially lethal adverse effects of checkpoint blockade represent another major challenge, the mechanisms of which remain poorly understood. Compared to the cancer signaling pathways, such as p53 and Ras, mechanistic studies on immune checkpoint pathways are still in their infancy. To improve the responses to checkpoint blockade therapy and limit the adverse effects, it is essential to understand the molecular regulation of checkpoint molecules in both malignant and healthy cells/tissues. This book begins with an introduction to immune checkpoint therapy and its challenges, and subsequently describes the regulation of checkpoints at different levels. In closing, it discusses recent therapeutic developments based on mechanistic findings, and outlines goals for future translational studies. The book offers a valuable resource for researchers in the cancer immunotherapy field, helping to form a roadmap for checkpoint regulation and develop safer and more effective immunotherapies.

Advances in anti-cancer chemotherapy over recent years have led to improved efficacy in curing or controlling many cancers. Some chemotherapy-related side-effects are well recognized and include: nausea, vomiting, bone marrow suppression, peripheral neuropathy, cardiac and skeletal muscle dysfunction and renal impairment. However, it is becoming clearer that some chemotherapy-related adverse effects may persist even in long term cancer survivors. Problems such as cognitive, cardiovascular and gastrointestinal dysfunction, and neuropathy may lead to substantial long term morbidity. Despite improvements in treatments to counteract acute chemotherapy-induced adverse effects, they are often incompletely effective. Furthermore, counter-measures for some acute side-effects and many potential longer term sequelae of anti-cancer chemotherapy have not been developed. Thus, new insights into prevalence and mechanisms of cancer chemotherapy-related side effects are needed and new approaches to improving tolerance and reduce sequelae of cancer chemotherapy are urgently needed. The present Research Topic focuses on adverse effects and sequelae of chemotherapy and strategies to counteract them.

Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field’s history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.