Topic
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.
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TL;DR: The properties and functions of wild‐type and mutant p53 will be compared and contrasted here and elsewhere within this thematic issue and the mechanisms of inactivation of p53 function will be discussed.
Abstract: Tumorigenesis is characterized by a series of genetic alterations in both dominant oncogenes and tumor suppressor genes. A hallmark of tumor suppressor genes is that both alleles are generally altered during transformation, which usually represents a loss of function phenotype. The p53 tumor suppressor gene is the most frequently affected gene detected in human cancer. There is now growing evidence suggesting that mutation of p53 may involve not only a loss of function of wild-type p53 activity but also a gain of function phenotype contributed by the mutant p53 protein. The study of the biological properties and functions of both wild-type and mutant p53 is central to our understanding of human cancer. These properties and functions of wild-type and mutant p53 will be compared and contrasted here and elsewhere within this thematic issue. In addition, the mechanisms of inactivation of p53 function, which include: 1) mutation, 2) inhibition by viral oncogene products, 3) inhibition by cellular regulators, and 4) alteration in subcellular localization, will be discussed.
434 citations
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TL;DR: Therapeutic strategies targeting the oncogenic consequences of p21 expression may provide a new approach to chemoprevention and treatment of cancer.
434 citations
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TL;DR: Aberrant Nrf2 activation provoked by Keap1 alteration is one of the molecular mechanisms for chemotherapeutic resistance in GBC and will be a novel therapeutic target as an enhancer of sensitivity to 5-FU-based regimens.
434 citations
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TL;DR: Emerging evidence indicating how cancer cells adopt various strategies to override apoptosis is discussed, including amplifying the antiapoptotic machinery, downregulating the proapoptosis program, or both.
433 citations
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TL;DR: A new mathematical model is developed for the somatic evolution of colorectal cancers that predicts that the observed genetic diversity of cancer genomes can arise under a normal mutation rate if the average selective advantage per mutation is on the order of 1%.
Abstract: Cancer results from genetic alterations that disturb the normal cooperative behavior of cells. Recent high-throughput genomic studies of cancer cells have shown that the mutational landscape of cancer is complex and that individual cancers may evolve through mutations in as many as 20 different cancer-associated genes. We use data published by Sjoblom et al. (2006) to develop a new mathematical model for the somatic evolution of colorectal cancers. We employ the Wright-Fisher process for exploring the basic parameters of this evolutionary process and derive an analytical approximation for the expected waiting time to the cancer phenotype. Our results highlight the relative importance of selection over both the size of the cell population at risk and the mutation rate. The model predicts that the observed genetic diversity of cancer genomes can arise under a normal mutation rate if the average selective advantage per mutation is on the order of 1%. Increased mutation rates due to genetic instability would allow even smaller selective advantages during tumorigenesis. The complexity of cancer progression can be understood as the result of multiple sequential mutations, each of which has a relatively small but positive effect on net cell growth.
432 citations