Ilar virus that could not [3,4]. Intriguingly, the SRC gene was detected in normal, uninfected avian tissue, unequivocally demonstrating that the origins of cancer are within us and that, in most cases, it is our own cellular genome that accumulates sufficient alterations to eventually lead to cancer. This discovery initiated an intense interest in understanding the human cancer genome and was enabled by an exponential development in molecular technology (see Meerzaman et al, this issue). At the time Sporn articulated his view of the characteristics or hallmarks of 3-Methyladenine web premalignant lesions, the diagnosis of cancer was largely based on pathologic characteristics. Today, pathological diagnoses are accompanied by a vast array of molecular detail [5,6]. Thus the question arises; can we leverage this molecular detail for the discrimination and “treatment” of premalignant conditions? In this special issue of Seminars in Oncology, we focus on the molecular properties of cells early in the carcinogenic process and how this informs the design of cancer prevention studies and selection of chemopreventive agents. In this review, we first discuss the molecular basis for cancer prevention and provide a few key AprotininMedChemExpress Aprotinin examples of how this knowledge has led to the development and implementation of cancer prevention strategies. Our goal is to (re-) acknowledge that although there is a continuum between premalignant and malignant lesions, they are two different entities [1] and with differing propensities for progression. We highlight a necessity to both study and recognize this distinction. Resolving the biological, molecular, and genetic hallmarks of cancer has entirely changed how we diagnose and treat cancer. Herein, we discuss the potential of leveraging this progress and paradigm for cancer prevention.Author Manuscript Author Manuscript Author Manuscript Author Manuscript2. The molecular basis for cancer prevention2.1. The hallmarks of cancer We know that whether from an underlying genetic predisposition, endogenous processes in the cell, bacterial or viral infection, and/or other exogenous factors such as sun, tobacco, certain chemical, or radiation exposure, it is our own cellular genome that collects enough genetic alterations to eventually transform a normal cell to a malignant one. Work by Vogelstein and others have shown us that many cancers have a natural history of progression, evolving from dysplasia to hyperplasia to in situ carcinoma and eventually to a malignant invasive tumor [7] (Fig. 1). To organize the growing volume of knowledge regarding the aberrant biology that characterizes cancer cells and to guide future studies of cancer biology, Hanahan and Weinberg first proposed the “Hallmarks of Cancer” framework in 2000 [8] (an updated version was published in 2011 [9]). The “Hallmarks of Cancer” proposal unifies the molecular pathways that contribute to the fundamental properties of cancer cells. The 2000 version of the “Hallmarks of Cancer” included: (1) selfsufficiency in growth signals; (2) insensitivity to anti-growth signals; (3) tissue invasion and metastasis; (4) limitless replication potential; (5) sustained angiogenesis; and (6) evadingSemin Oncol. Author manuscript; available in PMC 2017 February 01.Ryan and Faupel-BadgerPageapoptosis. In 2011, two emerging hallmarks–deregulating cellular energetics and avoiding immune destruction–and two enabling characteristics–genome instability and mutation and tumor inflammation–were added to.Ilar virus that could not [3,4]. Intriguingly, the SRC gene was detected in normal, uninfected avian tissue, unequivocally demonstrating that the origins of cancer are within us and that, in most cases, it is our own cellular genome that accumulates sufficient alterations to eventually lead to cancer. This discovery initiated an intense interest in understanding the human cancer genome and was enabled by an exponential development in molecular technology (see Meerzaman et al, this issue). At the time Sporn articulated his view of the characteristics or hallmarks of premalignant lesions, the diagnosis of cancer was largely based on pathologic characteristics. Today, pathological diagnoses are accompanied by a vast array of molecular detail [5,6]. Thus the question arises; can we leverage this molecular detail for the discrimination and “treatment” of premalignant conditions? In this special issue of Seminars in Oncology, we focus on the molecular properties of cells early in the carcinogenic process and how this informs the design of cancer prevention studies and selection of chemopreventive agents. In this review, we first discuss the molecular basis for cancer prevention and provide a few key examples of how this knowledge has led to the development and implementation of cancer prevention strategies. Our goal is to (re-) acknowledge that although there is a continuum between premalignant and malignant lesions, they are two different entities [1] and with differing propensities for progression. We highlight a necessity to both study and recognize this distinction. Resolving the biological, molecular, and genetic hallmarks of cancer has entirely changed how we diagnose and treat cancer. Herein, we discuss the potential of leveraging this progress and paradigm for cancer prevention.Author Manuscript Author Manuscript Author Manuscript Author Manuscript2. The molecular basis for cancer prevention2.1. The hallmarks of cancer We know that whether from an underlying genetic predisposition, endogenous processes in the cell, bacterial or viral infection, and/or other exogenous factors such as sun, tobacco, certain chemical, or radiation exposure, it is our own cellular genome that collects enough genetic alterations to eventually transform a normal cell to a malignant one. Work by Vogelstein and others have shown us that many cancers have a natural history of progression, evolving from dysplasia to hyperplasia to in situ carcinoma and eventually to a malignant invasive tumor [7] (Fig. 1). To organize the growing volume of knowledge regarding the aberrant biology that characterizes cancer cells and to guide future studies of cancer biology, Hanahan and Weinberg first proposed the “Hallmarks of Cancer” framework in 2000 [8] (an updated version was published in 2011 [9]). The “Hallmarks of Cancer” proposal unifies the molecular pathways that contribute to the fundamental properties of cancer cells. The 2000 version of the “Hallmarks of Cancer” included: (1) selfsufficiency in growth signals; (2) insensitivity to anti-growth signals; (3) tissue invasion and metastasis; (4) limitless replication potential; (5) sustained angiogenesis; and (6) evadingSemin Oncol. Author manuscript; available in PMC 2017 February 01.Ryan and Faupel-BadgerPageapoptosis. In 2011, two emerging hallmarks–deregulating cellular energetics and avoiding immune destruction–and two enabling characteristics–genome instability and mutation and tumor inflammation–were added to.