Therapeutic Opportunities And Innovative Biomarkers In Tumor Microenvironment

This book reviews different aspects of the cancer microenvironment, and its regulation and importance for tumor progression. Practical applications, in terms of how biomarkers are increasingly included in therapy protocols, will also be discussed. Biomarkers of the Tumor Microenvironment: Basic Studies and Practical Applications is aimed at research pathologists in the cancer field, and also cancer researchers from other backgrounds, especially those using morphology techniques and models focusing on cross-talk between different cell types in tumors.

This book reviews different aspects of the cancer microenvironment, and its regulation and importance for tumor progression. Methodological advancements and practical applications, in terms of how biomarkers are studied and increasingly included in clinical trials and therapy protocols, are described and discussed. Biomarkers of the Tumor Microenvironment is an educational resource for students and members of the cancer research community as a whole, especially for those using morphology analysis techniques and models focusing on the cross-talk between different cell types in tumors. The textbook provides a comprehensive overview of the microenvironment in various contexts from the perspectives of experienced and accomplished cancer researchers and clinicians.

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.

The way a cell undergoes malignant transformation should meet their capacity of surviving in the microenvironment of the organ where the cancer will develop. Metabolic adaptation is for sure one of the criteria that must be accomplished, driven by metabolic plasticity that allows the adaptation of cancer cells to the availability of energy and biomass sources that will sustain cell survival and proliferation. Each human organ has a particular microenvironment which depends on several cell types and in some cases also on symbiotic microorganisms. These biological partners are constantly sharing organic compounds and signaling molecules that will control mitogenesis, cell death and differentiation, accounting for the organ's function. Nevertheless, cancer cells are capable of taking advantage of this metabolic and signaling microenvironmental dynamics. In this book, we intend to present the different components of the microenvironment driving the metabolic fitness of cancer cells. The metabolic changes required for establishing a tumor in a given microenvironment and how these metabolic changes limit the response to drugs will generally be the major items addressed. It is important to mention not only aspects of the microenvironment that stimulate metabolic changes and that select better adapted tumor cells, but also how this regulation of cell plasticity is made. Thus, the signaling pathways that orchestrate and are orchestrated throughout this panoply of metabolic rearrangements will also be addressed in this book. The subjects will be presented from the conceptual point of view of the cross-cancer mechanisms and also particularizing some models that can be examples and enlightening within the different areas.

This comprehensive book provides an overview of cancer therapeutics and covers different innovative treatment approaches for cancer. The initial chapter gives a detailed overview on cancer progression and disease diagnostics. The following chapters focus on different cancer treatment approaches, such as chemotherapy, radiotherapy, hormonal therapy, immunotherapy, nutritional assessments, targeted therapy and Nano therapeutics. It also highlights the importance of cancer genomics, disease advancement, personalized medicine and psychological support for cancer patients. Emphasis is also given to the many challenges in the area of designing cancer treatment and designing clinical trials. The complete book also presents cancer management with different cancer treatment modalities, including pharmacogenomics and drug reactions. This is a unique and comprehensive piece of work that not only highlights the disease treatment modalities but also focuses on many challenges in the area of designing cancer treatment and even in designing clinical trials. The contributing authors are experts in this field of cancer treatment. By familiarizing readers with the latest developments in this complex field, the book offers a valuable resource for clinicians. Researchers and medical students will also benefit from this comprehensive text.

This book will allow readers to discover the crucial role of tumor microenvironment (TME) in the selection of cancer cells that are more prone to carry on cancer initiation and progression. The metabolic remodeling, as the basis of life overall, allows the adaptive establishment of a tumor in a certain TME, which in turn presents a variety of selective pressures. Coupled with the late diagnosis, the poor therapy response are the main hurdles limiting oncological disease control and eventual cure. Thus the metabolic plasticity of cancer cells often underlies chemoresistance. This edited work presents an exhaustive description and comprehensive view of cancer metabolism as a weapon used by cancer cells to adapt to TME. TME and the organ microenvironment is analyzed as a whole, considering cancer cells, stromal cells and microbiota. This complex circuit is observed as the support for disease development and therapy evasion but also as a valuable kernel, presenting new players to be targeted in a more precise cancer therapy. The various threads of cancer biology related to TME and metabolic adaptation will be addressed including: 1) key players in the metabolic network; 2) the way adaptive metabolic features are sustained by TME; 3) TME and metabolic signaling, accounting for cancer cells survival; 4) metabolic fitness driven limitations in therapy response, and 5) the way TME and cancer metabolism can be helpful in the design of new drugs. In addition, the usefulness, technical strengths and weaknesses of analytical techniques useful in cancer metabolomics will be presented in an integrative way. Moreover, the use of innovative and traditional in vitro and in vivo cancer models, as powerful tools to address the influence of TME in cancer progression and metabolic reprogramming will be also presented. This work was written by experts and dedicated to researchers with interests in cancer biology, TME, cancer metabolism and therapy. It will interest the Advances in Experimental Medicine and Biology readership, including basic researchers, analytic researchers, bio-engineers and clinicians.

Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

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.

Nowhere is the explosion in comprehensive genomic testing more evident than in oncology. Multiple consensus guidelines now recommend molecular testing as the standard of care for most metastatic tumors. To aid in the advancement of this rapidly changing field, we intend this Special Issue of JPM to focus on technical developments in the genomic profiling of cancer, detail promising somatic alterations that either are, or have a high likelihood of being, relevant in the near future, and to address issues related to the pricing and value of these tests.The last few years have seen the cost of molecular testing decrease by orders of magnitude. In 2018, we saw the first “site-agnostic” drug approvals in cancer (for microsatellite unstable cancer (PD-1 inhibitors) and NTRK-fusions (TRK inhibitors)). Research on targetable mutations, determination of genetic “signatures” that can use multiple individual genes/pathways, development of targeted therapy, and insight into the value of new technology remains at the cutting edge of research in this field. We are soliciting papers that present new technologies to assess predictive biomarkers in cancer, original research (pre-clinical or clinical) that demonstrates promise for particular targeted therapies in cancer, and articles that explore the clinical and financial impacts of this paradigmatic shift in cancer diagnostics and treatment.