Plant Flavonoids Against Metastasis: New Concepts For Cancer Treatment

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 tumor 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 tumor 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 tumors 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 tumor 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 tumors 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 tumor 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 signaling cascades in different tumor cells, and also modulate diverse components of tumor microenvironments and attenuate the formation of tumor-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.