Immunotherapy and Cancer Therapeutics: A Rich Partnership

doi:10.1016/B978-0-12-394296-8.00025-7

Cancer Immunotherapy (Second Edition)

Immune Suppression and Tumor Growth

2013, Pages 415-432

https://doi.org/10.1016/B978-0-12-394296-8.00025-7 Get rights and content

Abstract

Cancer is managed by surgery, radiation therapy, and systemic drug therapies. Drug therapies include endocrine manipulation, single- or multi-agent chemotherapy, and monoclonal antibody therapy. Targeted small molecules that specifically capitalize on vulnerabilities that map to signaling pathways indispensible for tumor growth and progression are now also a part of the standard of cancer care. More recently, rapidly accumulating data illustrates a critical role for the immune system in the response to chemotherapy, radiation (the abscopal effect), and novel targeted cancer therapies. Integrating immune-based therapies strategically with established and novel cancer therapeutics should generate a robust antitumor effect that takes advantage of the strengths of their individual modes of action and also leverages potential immunologic synergies.

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For many centuries surgery is the most commonly used cancer management. However curing knew that cancer would come back, with such an invasive method. For this reason, the use of therapeutics were engaged with this need. In the 19th century, regressive effects of hormone therapy on breast and prostate cancers were assessed. The invention of X-rays led to the use of radiation in cancer treatment. After a while, the cancer-causing effect of radiation was recognized and a need for new methodologies arose. For this reason, proton beams were used instead of X-ray radiation and chemical modifiers were developed, both to sensitize tumor cells to radiation and to protect normal cells. Chemical agents have been used since it was noticed during World War II, that they could kill cancer cells by damaging their DNA. Over time, novel chemotherapeutics were designed with minimum side effects and to maximum activity. Synchronous with the improvement of knowledge on cell biology, immunotherapeutic agents were engaged that could mimic normal cell growth process. However, because all these therapeutics have a mortal effect both on healthy and cancer cells, targeted therapies should be preferred. Targeted therapies act by affecting the pathways responsible in cell growth, division, and spread of cancer cells. Following scientific and technological developments, new approaches have arisen, such as gene-therapy, stem cell therapy, immunotherapy, and nanotechnology derived therapies. Combination of chemotherapeutic with nanoparticles is a novel approach that is being used in the treatment of cancer. With the development of imaging technologies and diagnostic methods, many cancer types may be detected in much earlier stages. The more cancer signaling pathways are determined, the better the diagnostics and therapies will be achieved.
Topics in this chapter can be summarized as surgical resection, radiation therapy, chemotherapy, ımmunotherapy, novel and target-specific therapies, and future perspectives. The main aim of this chapter is not to give exact information about survey of the current studies in this area since it is not possible to reach whole information of preclinical or clinical research.
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Citation Excerpt :
The revolution of biotechnology has led to the creation of various types of therapeutic proteins (Brown, 2005; Xie et al., 2008; Almeida and Souto, 2007; Tan and Danquah, 2012; Stevenson et al., 2012; Ye et al., 2010; Torchilin and Lukyanov, 2003), with the potential to provide treatment for certain dangerous diseases that have long been thought incurable (Brown, 2005). Biotherapy now has the potential to target chronic and malignant diseases such as cancer (Dougan and Dranoff, 2012; Jaffee, 1999; Chen et al., 2013; Rossi et al., 2013a), dwarfism (Matiasevic and Gershberg, 1966), AIDS (Tomasselli and Heinrikson, 2000), autoimmune disorders (Almeida and Souto, 2007), etc. Moreover, proteins can be used to detect and diagnose diseases (Gelfand, 2001; Hj, 1983) in addition to using proteins as vaccines in order to ensure protection from various diseases (Rossi et al., 2013b; Chura-Chambi et al., 2014).
Proteins are a vital constituent of the body as they perform many of its major physiological and biological processes. Recently, proteins and peptides have attracted much attention as potential treatments for various dangerous and traditionally incurable diseases such as cancer, AIDS, dwarfism and autoimmune disorders. Furthermore, proteins could be used for diagnostics. At present, most therapeutic proteins are administered via parenteral routes that have many drawbacks, for example, they are painful, expensive and may cause toxicity. Finding more effective, easier and safer alternative routes for administering proteins and peptides is the key to therapeutic and commercial success. In this context, much research has been focused on non-invasive routes such as nasal, pulmonary, oral, ocular, and rectal for administering proteins and peptides. Unfortunately, the widespread use of proteins and peptides as drugs is still faced by many obstacles such as low bioavailability, short half-life in the blood stream, in vivo instability and numerous other problems. In order to overcome these hurdled and improve protein/peptide drug efficacy, various strategies have been developed such as permeability enhancement, enzyme inhibition, protein structure modification and protection by encapsulation. This review provides a detailed description of all the previous points in order to highlight the importance and potential of proteins and peptides as drugs.
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Chapter 25 - Immunotherapy and Cancer Therapeutics: A Rich Partnership

Abstract