Tumor Microenvironment And Cancer Therapy

It is well established that the tumor microenvironment(TME) plays a pivotal role in tumor initiation, progression and therapeutic resistance by creating a dynamic interaction with cancer cells. TME is comprised of extracellular matrix (ECM), growth factors, nutrients, blood and lymphatic vessels, and non-cancer stromal cells, which serve as a sustained niche for cancer cells to proliferate and metastasize. Notably, various cellular components in TME, including endothelial cells, fibroblasts, pericytes, adipocytes, immune cells, cancer stem cells, and vasculature, could promote tumor’s immune evasion and growth.

This book addresses the biological processes relevant to the immune phenotypes of cancer and their significance for immune responsiveness, based on the premise that malignant cells manipulate their surroundings through an evolutionary process that is controlled by interactions with innate immune sensors as well as the adaptive recognition of self/non-self. Checkpoint inhibitor therapy is now an accepted new form of cancer treatment. Other immuno-oncology approaches, such as adoptive cell therapy and metabolic inhibitors, have also shown promising results for specific indications. Immune resistance is common, however, limiting the efficacy of immunotherapy in many common cancer types. The reasons for such resistance are diverse and peculiar to the immune landscapes of individual cancers, and to the treatment modality used. Accordingly, approaches to circumvent resistance need to take into account context-specific genetic, biological and environmental factors that may affect the cancer immune cycle, and which can best be understood by studying the target tissue and correlated systemic immune markers. Understanding the major requirements for the evolutionary process governing human cancer growth in the immune-competent host will guide effective therapeutic choices that are tailored to the biology of individual cancers.

In the post-genomic era, cancer is a genetic disease. However, cancer genotype does not always equal cancer phenotype. Cancers with the same genetic abnormalities don’t always behave the same. Understanding and eradicating cancers will require an appreciation for cancer’s ecology. This book is the first to comprehensively explore and critically appraise cancer microenvironments and host interactions with an eye towards exploiting our understanding for new treatments. The team of contributors share amongst them impressive experiences at the laboratory bench and in the clinic. These physician-scientists have dedicated themselves to the tension between the urgency for cures and the technical challenges of discovery. The target audience includes clinical oncologists, clinical hematologists, research oncologists, research hematologists, immunologists, stem cell researchers, oncology and hematology fellows (trainees), oncology educators (graduate and undergraduate levels), and course book for graduate students and undergraduate students.

The tumor microenvironment has become a very important and hot topic in cancer research within the past few years. The tumor microenvironment is defined as the normal cells, molecules, and blood vessels that surround and feed a tumor cell. As many scientists have realized, studying the tumor microenvironment has become critical to moving the field forward, since there are many players in a tumor’s localized and surrounding area, which can significantly change cancer cell behavior. There is a dual relationship wherein the tumor can change its microenvironment and the microenvironment can affect how a tumor grows and spreads. Tumor Microenvironment in Cancer Progression and Cancer Therapy aims to shed light on the mechanisms, factors, and mediators that are involved in the cancer cell environment. Recent studies have demonstrated that in addition to promoting tumor progression and protecting tumor cells from the spontaneous immune-mediated rejection and different forms of cancer therapeutics, tumor microenvironment can also be a target and mediator of both standard and newly-emerging forms of cancer therapeutics. Thus, the dual role of the tumor microenvironment is the integral focus of the volume. The volume highlights the bi-directional interactions between tumor cells and non-malignant tumor component during tumor progression and treatment. It also focuses on the three groups of the reactive tumor component: stromal cells, blood vessels and the infiltrating immune cells. These three groups are discussed under the lens of their role in promoting tumor growth, shielding the tumor from rejection and from standard forms of cancer therapies. They are emerging as targets and mediators of standard and new forms of potential therapy.

This book proposes the importance of new systems of drug design and delivery based on cancer pathophysiology in addition to cancer molecular and cellular biology. The current studies based on molecular and cellular biology while ignoring pathophysiology and pharmacology may be leading the development of antitumor drugs in the wrong direction and wasting a lot of money. Although there have been numerous reports of genetic and phenotypic changes in tumors, a large body of pathological and clinical evidence supports the conclusion that there are no pivotal changes in tumor cells that distinguish them consistently and reliably from normal dividing cells. Unlike using antibiotics against bacterial infection, therefore, anticancer agents (ACAs) need to be delivered selectively to tumor tissues and should be kept there long enough to reproduce the concentrations they reach in the Petri dish, which is a closed space where the cytocidal effects of any anticancer agents (ACAs) including molecular targeting agents are very strong. In the body, however, administered ACAs are cleared with the passage of time. Furthermore, most human cancers possess abundant stroma that hinders the penetration of drugs into the tumor microenvironment. Therefore, to overcome these difficulties, novel drug delivery systems have been designed, such as nanoparticles and ACA conjugated antibodies to stromal components and to cancer cell surface antigens. These advances are described in this book after the first section, which describes core features of the pathophysiology of the cancer microenvironment, on which these new developments are based.

Cancer cells can change and adapt, especially within the host environment; a phenomenon known as cancer plasticity. Several factors, including the immune system can influence, and be influenced by, cancer plasticity which in turn can impact upon patient responses to treatment. As such, we currently face several challenges for implementing combination therapies as effective cancer treatment strategies. We have compiled a topic with a number of articles that emphasize the various aspects of cancer plasticity, describing in particular the important role of the tumor microenvironment. As we embark on a new era of precision medicine with multi-modal therapies for improving patient outcomes, this topic highlights some relevant points for consideration that are pertinent to the incorporation and effective use of new treatments as part of cancer treatment regimens, including immune-modulating drugs.