Cancer poses a major threat to human health and is one of the leading causes of death worldwide. Today, we know that metastasis, a multistep process whereby tumour cells spread from the site of origin to distant organs, is responsible for most cancer mortality. In fact, more than 90% of cancer-related deaths are attributed to tumour metastasis. Unfortunately, there are no therapies currently available to specifically target metastasis of any human cancer types, and patients with distant metastases ultimately die from their disease. Current conventional treatment modalities are focused on the removal of tumours by surgical resection and/or the killing of malignant cells using cytotoxic chemotherapeutic drugs or ionizing radiation, with no substantial inhibitory effects on the migratory and invasive abilities of cancer cells. Moreover, emerging evidence has shown that these standard treatment modes can unexpectedly increase the motility and invasiveness of surviving tumour cells, inducing or accelerating metastases formation and aggravating malignant progression. This paradoxical phenomenon can help us to understand why, despite the technological advancements in surgical procedures and drug delivery methods, the overall survival rate of numerous cancer types has barely changed over the past several decades, remaining unacceptably poor. Due to the insufficiency of existing therapies in improving the prognosis of cancer patients, new effective treatment options are urgently needed. To this end, the focus must be moved from a simply cytotoxic approach to s metastasis-preventing strategy, substituting the question of why cancer forms and how to kill it for the question of why tumours spread and how to prevent metastasis. In this book, a conceptually new approach to cancer management is presented, by focusing not on the killing of transformed neoplastic cells, but blocking the spread of tumour cells to distant organs, thereby restricting malignant progression and targeting the main cause of cancer-related mortality. Plant-derived flavonoids might be ideal candidates for novel antimetastatic agents, as they are non-toxic and possess the capacity to inhibit multiple steps of metastatic cascade. These polyphenolic phytochemicals act through regulating a number of metastasis-associated signalling cascades in different tumour cells, and also modulate diverse components of tumour microenvironments and attenuate the formation of tumour-specific angiogenesis. Moreover, the combination of certain flavonoids with surgical resection, chemotherapy or radiotherapy may result in the abolishment of the metastasis-promoting effects of these conventional therapeutic modalities, providing novel treatment options for combating cancer in the future. It is expected that the development of flavonoids for antimetastatic drugs and their inclusion in further cancer treatment strategies can substantially improve the prognosis of patients with various types of malignancies in a time when cancer incidence is predicted to continuously increase throughout the world. This book should be read by anyone who is interested in innovative advances in cancer care. Due to its systemic approach to cellular and molecular processes of metastatic cascade, this book might serve as a useful contemporary textbook for medical colleges and universities for studies of cancer development, progression and dissemination.

In parallel with the continuous rise of cancer incidence, efficient treatment becomes an increasingly important public health concern. Radiotherapy has remained one of the most important anticancer approaches for clinical management of a variety of human tumours, as at least half of all oncological patients receive this therapy at some stages of their disease. With the hope to attain greater anticancer response, the interest in using natural plant-derived products as complementary treatments to conventional radiotherapy has substantially increased in the recent years. However, the interactions between phytochemicals and ionizing radiation are not always known and can be often unpredictable. Therefore, in this book, the current findings about the combined treatments of malignant cells with radiation and flavonoids, the largest group of human dietary plant polyphenols, are described. These data show that under carefully chosen dosage-schedule regimens, certain flavonoids or their natural mixtures can behave as potent radiosensitizers, augmenting radiotherapeutic efficacy in different preclinical cancer models. Such radio-sensitising action of flavonoids can be achieved through modulation of the redox status and suppression of several cellular survival pathways activated by radiotherapy, ultimately leading to the death of malignant cells. As flavonoids can concurrently protect normal healthy cells from irradiation-induced injury and thereby minimize toxic adverse reactions, use of these plant-derived agents as complementary approach to radiotherapy might open new avenues for enhancement of clinical outcome. Therefore, combining conventional anticancer modalities with conscious intake of flavonoid supplements as adjuvant agents might be an important future strategy to boost the therapeutic success in the treatment of various human malignancies.

Despite intensive work on molecular carcinogenic mechanisms and novel drug development, cancer has still remained an incurable disease. With the hope to gain therapeutic advantage or miracle cure, more than 50% of cancer patients consume various kinds of herbal supplements when undergoing chemotherapeutic treatment with antineoplastic agents. However, numerous preclinical studies on combined treatment of various cancer cells with natural dietary flavonoids and chemotherapeutic drugs have revealed both desired (additive to synergistic) as well as undesired (antagonistic) interactions, meaning that coadministration of flavonoids and chemotherapeutic drugs can lead to both augmentation as well as abolishment of therapeutic efficacy. This book is the first one to systematically compile currently available information about the modulation of chemotherapeutic efficacy by flavonoids, hopefully being an assistant for cancer patients to make conscious choices in selecting proper plant products during chemotherapeutic treatment.

Flavonoids are plant secondary metabolites with a basic polyphenolic skeleton and anticancer properties have greatly attracted the interest of scientists already for several years. This structurally diverse group of phytochemicals can be found abundantly in various edible plant products, such as fruits and vegetables, tea and cocoa, nuts, spices, grains and medicinal herbs. In the past decades, numerous experimental studies have shown antiproliferative, proapoptotic, antiinflammatory, antiangiogenic, antiinvasive and antimetastatic activities of these compounds in different cancerous systems. Because of close contacts and interactions of ingested food components with the epithelial lining of organ sites of the upper gastrointestinal tract, flavonoids can directly affect the development and progression of malignant neoplasms in the oral cavity, esophagus and stomach. This book gives a comprehensive and contemporary survey about the different anticancer actions of various natural and semisynthetic flavonoids in experimental models of oral, pharyngeal, esophageal and gastric cancers, involving the data obtained from studies of both cell lines as well as laboratorial animals. Also, the effects of flavonoids on the therapeutic responses of conventional cancer treatment modalities, i.e., different chemotherapeutic drugs and irradiation, are presented and analyzed. Moreover, the current epidemiological knowledge about the role of dietary intake of flavonoids on the risk of carcinogenesis in the upper digestive tract in populations with different dietary and lifestyle habits is described. By virtue of the high topicality of the subject but also the thoroughness of its discussion, this book could be interesting and attractive to basic scientists working in the field of plant chemicals, molecular cancer research or design and development of novel anticancer drugs; synthetic chemists in different pharmaceutical companies; health workers and nutritional counselors; medical doctors working with cancer patients; people suffering from any type of upper digestive tract tumors and their family members; and anyone who is interested in the natural tools for the fight against malignant neoplasms and whose purpose is to consciously prevent carcinogenesis within the upper gastrointestinal tract.

Cancer is a serious and ever-growing health concern not only in humans but also in dogs. Considering the differences in average lifespans, people commonly experience the loss of their companion dogs, representing a traumatic event to pet owners. On the one hand, better nutrition and improved care with many recent advancements in veterinary medicine have allowed dogs to live longer. On the other hand, this has involved an increased prevalence of aging-related diseases, including different types of malignancies. In fact, cancer afflicts one in every three dogs, being the most common cause of canine death. Hence, dogs with cancer require treatment, but differently from the human oncology, there are only few established standards of care for clinical management of canine tumours, besides the lack of effective drugs. Research into identification of novel efficient anticancer compounds and development of new therapeutic options are therefore highly needed to help man's best friend in combating malignant neoplasms. Over the past few decades, researchers have paid attention to the health benefits of various plant secondary metabolites, leading to the development of several new drugs for human medicine. Proceeding from this success, in this book, the current knowledge about anticancer effects of plant-derived compounds in different canine cancer models is compiled, discussing the role of phytochemicals in vitro canine cancer cell lines, in vivo xenografted mice, and in tumour-bearing dogs. Although still limited, these data reveal a great potential of plant compounds in reducing proliferation and inducing death of cells derived from different types of canine tumours, allowing these natural substances to be considered as promising anticancer drug candidates for dogs. This approach can not only result in the development of more efficient therapeutic agents for canine oncology in the future, but also provide new possibilities for chemopreventive strategies. Finally, considering the high biological, histological, and clinical similarities between canine and human tumours, knowledge on bioactivities of specific phytochemicals in cancer-bearing dogs can ultimately benefit both species, accelerating drug development paths for humans and promoting general advancement of oncological discipline.