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.

Tumor microenvironment (TME) refers to the area with non-malignant cells, signaling molecules and blood vessels that surrounds and feeds tumor cells. A tumor can change its microenvironment, and TME is also known to profoundly impact the occurrence, growth, metastasis and therapeutic response and resistance of tumors. The special paracrine characteristics, microvascular system, extracellular matrix components and stromal cells in TME promote local tumor immune suppression and could alter the penetration and distribution of drugs into tumor tissues. Accumulating evidence demonstrates that currently available tumor therapies (i.e., chemotherapy, radiotherapy, anti-vascular therapy, small molecule targeted therapy, immune checkpoint inhibitors) also in turn greatly affect the structure, function, and physical and chemical properties of TME, leading to TME remodeling. However, whether and how interaction of tumor cells and TME modeling can be dissected and targeted to further understand the underlying molecular mechanisms and establish effective new tumor therapies remains elusive.

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.

Metabolic reprogramming is the hallmark of malignant tumors. Both metabolic phenotype and metabolic dependence are changed during the development of cancer from precancerous tissue to local invasion to metastasis. Cancer cells autonomously alter their flux through various metabolic pathways in order to meet the increased bioenergetic and biosynthetic demand as well as mitigate oxidative stress required for cancer cell proliferation and survival. The change of the tumor microenvironment (TME) is a key factor driving tumor metabolic reprogramming. The tumor microenvironment denotes the non-cancerous cells and components presented in the tumor, including molecules produced and released by them. The constant interactions between tumor cells and the tumor microenvironment play decisive roles in tumor initiation, progression, metastasis, and response to therapies. More and more evidence has pointed out that the change in the tumor microenvironment is a key factor driving tumor metabolic reprogramming. However, the specific relationship between tumor metabolic reprogramming and tumor microenvironment remains unclear. Indeed, emerging evidence indicates that cancer cells are able to suppress the anti-tumor immune response by competing for and depleting essential nutrients or otherwise reducing the metabolic fitness of tumor-infiltrating immune cells. The actual process of how metabolic reprogramming and cancer immune response affect each other has not been understood.

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.

Role of Tumor Microenvironment in Breast Cancer and Targeted Therapies discusses the current understanding of breast cancer tumor microenvironment components, their role in tumorigenicity and the development of therapeutic resistance, along with updates on recent advances. - Presents up-to-date knowledge on the interplays of stromal components surrounding breast tumor cells - Explores recent advances and trends in the molecular mechanisms of breast tumorigenesis and how to explore further molecular targets