Carcinogenesis

About: Carcinogenesis is a research topic. Over the lifetime, 60368 publications have been published within this topic receiving 3192599 citations. The topic is also known as: oncogenesis & tumorigenesis.

Mutation and Cancer: A Model for Human Carcinogenesis

Abstract: A model for carcinogenesis is presented that provides a framework for understanding the roles of "spontaneous" events, hereditary factors, and environmental agents in human carcinogenesis and for interpreting experimental carcinogenesis. This model incorporates two features: a) transition of target stem cells into cancer cells via an intermediate stage in two irreversible steps, and b) growth and differentiation of normal target and intermediate cells. Cast in mathematical terms, the model can be fitted to age-specific incidence data on human cancers of both children and adults and can illuminate the relative importance of agents that affect transition rates, tissue growth, and tissue differentiation. This is illustrated by application of the model to a) the epidemiology of lung cancer with emphasis on the role of cigarette smoking and b) the epidemiology of breast cancer with emphasis on the roles of hormones, radiation, and hereditary. The nature of the two events and of the intermediate stage is considered in light of hereditary conditions that predispose to cancer in humans. The modes of action of radiation and chemicals in carcinogenesis are discussed, as are predictions based on the model and amenable to experimental verification.

The Biology of Cancer Stem Cells

Abstract: Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies.

The inhibitors of apoptosis (IAPs) and their emerging role in cancer.

Abstract: The inhibitor of apoptosis protein family has been characterized over the past 5 years, initially in baculovirus and more recently in metazoans. The IAPs are a widely expressed gene family of apoptotic inhibitors from both phylogenic and physiologic points of view. The diversity of triggers against which the IAPs suppress apoptosis is greater than that observed for any other family of apoptotic inhibitors including the bcl-2 family. The central mechanisms of IAP apoptotic suppression appear to be through direct caspase and pro-caspase inhibition (primarily caspase 3 and 7) and modulation of and by the transcription factor NF-κB. Although evidence for a direct oncogenic role for the IAPs has yet to be delineated, a number of lines of evidence point towards this class of protein playing a role in oncogenesis. The strongest evidence for IAP involvement in cancer is seen in the IAP called survivin. Although not observed in adult differentiated tissue, survivin is present in most transformed cell lines and cancers tested to date. Survivin has been shown to inhibit caspase directly and apoptosis in general, moreover survivin protein levels correlate inversely with 5 year survival rates in colorectal cancer. Recent data has also implicated survivin in cell cycle control. The second line of evidence for IAP involvement in cancer comes from their emerging role as mediators and regulators of the anti-apoptotic activity of v-Rel and NF-κB transcription factor families. The IAPs have been shown to be induced by NF-κB or v-Rel in multiple cell lines and conversely, HIAP1 and HIAP2 have been shown to activate NF-κB possibly forming a positive feed-back loop. Overall a picture consistent with an IAP role in tumour progression rather than tumour initiation is emerging making the IAPs an attractive therapeutic target.

MicroRNA-Cancer Connection: The Beginning of a New Tale

Abstract: Cancer initiation and progression can involve microRNAs (miRNA), which are small noncoding RNAs that can regulate gene expression. Their expression profiles can be used for the classification, diagnosis, and prognosis of human malignancies. Loss or amplification of miRNA genes has been reported in a variety of cancers, and altered patterns of miRNA expression may affect cell cycle and survival programs. Germ-line and somatic mutations in miRNAs or polymorphisms in the mRNAs targeted by miRNAs may also contribute to cancer predisposition and progression. We propose that alterations in miRNA genes play a critical role in the pathophysiology of many, perhaps all, human cancers.