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Proceedings of the National Academy of... Sep 2016Prevention is an essential component of cancer eradication. Next-generation sequencing of cancer genomes and epigenomes has defined large numbers of driver mutations and...
Prevention is an essential component of cancer eradication. Next-generation sequencing of cancer genomes and epigenomes has defined large numbers of driver mutations and molecular subgroups, leading to therapeutic advances. By comparison, there is a relative paucity of such knowledge in premalignant neoplasia, which inherently limits the potential to develop precision prevention strategies. Studies on the interplay between germ-line and somatic events have elucidated genetic processes underlying premalignant progression and preventive targets. Emerging data hint at the immune system's ability to intercept premalignancy and prevent cancer. Genetically engineered mouse models have identified mechanisms by which genetic drivers and other somatic alterations recruit inflammatory cells and induce changes in normal cells to create and interact with the premalignant tumor microenvironment to promote oncogenesis and immune evasion. These studies are currently limited to only a few lesion types and patients. In this Perspective, we advocate a large-scale collaborative effort to systematically map the biology of premalignancy and the surrounding cellular response. By bringing together scientists from diverse disciplines (e.g., biochemistry, omics, and computational biology; microbiology, immunology, and medical genetics; engineering, imaging, and synthetic chemistry; and implementation science), we can drive a concerted effort focused on cancer vaccines to reprogram the immune response to prevent, detect, and reject premalignancy. Lynch syndrome, clonal hematopoiesis, and cervical intraepithelial neoplasia which also serve as models for inherited syndromes, blood, and viral premalignancies, are ideal scenarios in which to launch this initiative.
Topics: Germ Cells; Humans; Immune System; Models, Biological; Neoplasm Proteins; Neoplasms; Precancerous Conditions; Tumor Microenvironment
PubMed: 27638202
DOI: 10.1073/pnas.1608077113 -
Diseases of the Colon and Rectum Apr 2001A 40-year-old man with ganglioneuromatous polyposis and an aggressive coexisting colorectal cancer is described. Contrary to previous reports, we believe that... (Review)
Review
A 40-year-old man with ganglioneuromatous polyposis and an aggressive coexisting colorectal cancer is described. Contrary to previous reports, we believe that ganglioneuromatous polyposis should be considered a premalignant condition.
Topics: Adenocarcinoma; Adenoma; Adult; Colorectal Neoplasms; Ganglioneuroma; Humans; Intestinal Polyps; Male; Precancerous Conditions
PubMed: 11330589
DOI: 10.1007/BF02234335 -
The Australasian Journal of Dermatology Aug 1995Cryosurgical treatment of skin cancer and premalignant conditions of the skin has been in widespread use for 20 years. Data accumulated over this period suggest that if... (Review)
Review
Cryosurgical treatment of skin cancer and premalignant conditions of the skin has been in widespread use for 20 years. Data accumulated over this period suggest that if attention is paid to the treatment technique and to lesion selection, then cure rates equivalent to radiotherapy, simple surgical excision, and curettage and cautery can be achieved reliably. Moh's micrographic surgery offers a higher cure rate for skin cancer, but is not suitable for the vast majority of lesions seen in clinical practice. The decision to use cryosurgery to treat any particular lesion will therefore be influenced by a number of other considerations. Cryosurgery competes well on morbidity and cosmetic outcome and is the quickest, easiest, cheapest and most readily available of the treatment options. As such it has earned its place among the recognized treatment modalities for skin cancers as well as premalignant conditions of the skin. Cryosurgery is commonly delivered empirically without record of the dose delivered and without audit of the outcome. The aim of this review is to describe in detail one standard technique of therapy that is easily reproduced and has been audited; the timed spot freeze technique. This technique can be used, even by those inexperienced in cryosurgery, to achieve predictable success rates. Many other techniques do exist, but either have not been audited or are unnecessarily cumbersome.
Topics: Carcinoma, Basal Cell; Cryosurgery; Female; Humans; Male; Postoperative Complications; Precancerous Conditions; Skin Neoplasms; Ultrasonography
PubMed: 7487739
DOI: 10.1111/j.1440-0960.1995.tb00955.x -
Scandinavian Journal of Urology and... 2000Bladder cancer is believed to develop through reversible premalignant stages followed by irreversible steps, and ending in invasive cancer giving rise to distant... (Review)
Review
Bladder cancer is believed to develop through reversible premalignant stages followed by irreversible steps, and ending in invasive cancer giving rise to distant metastases. Because of the variation in the clinical course it has also been suggested that different forms of cancer develop along different molecular pathways leading to tumor presentations of various malignant potential. Today we treat and prognosticate bladder cancer on the basis of clinical and histologic findings that are insufficient to assess all the biologic potential of these tumors. Understanding the pathogenesis of bladder cancer might lead to a more precise identification of particular tumors with regard to clinical aggressiveness, resulting in individualized strategies for treatment and prophylaxis. Bladder cancer is seldom diagnosed in its preclinical stage, it is instead detected at cystoscopy and virtually never recognized as an incidental finding on autopsy. Therefore its "natural history" largely reflects that of "treated" disease. The true incidence of premalignant and malignant epithelial changes is not known. Incidences of hyperplasia and dysplasia of approximately 10% and approximately 5%, respectively and only occasional findings of cancer itself were reported in two autopsy series. Urothelial dysplasia is generally believed to be premalignant and a putative precursor of invasive cancer but unfortunately there has been a lack of standardization in terms of terminology and diagnosis. There is also a need for an agreed definition of the boundary between premalignancy, i.e. urothelial changes that have some but not all the features of carcinoma in situ, and malignancy, especially when considering potentially harmful treatments to prevent this transition. Most new diagnostic tools available and being tested today compare new detection techniques with traditional methods such as cytology or conventional histology of malignant rather than premalignant changes. There is probably also a short preclinical latency, as implied by the incidental findings of bladder cancer at autopsy, which makes it necessary to define how and when to promote early detection and treatment. Future studies therefore have to concentrate on methods for early detection of disease as well as characterization of host susceptibility, evaluation of exposure to carcinogens and potential effects of preventive measures. It is also likely that the improved tools of molecular prognostication will allow us to design trials more precisely in order to tailor therapeutic strategies.
Topics: Animals; Anticarcinogenic Agents; Carcinoma in Situ; Carcinoma, Transitional Cell; Humans; Neoplasm Staging; Precancerous Conditions; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 11144892
DOI: 10.1080/00365590050509878 -
Journal of the California Dental... Aug 2001A premalignant phase in the development of oral cancer is predicted by the classic model of experimental epithelial carcinogenesis. Virtually all oral squamous cell...
A premalignant phase in the development of oral cancer is predicted by the classic model of experimental epithelial carcinogenesis. Virtually all oral squamous cell carcinomas arise from a premalignant precursor, but it is difficult to specifically define the term premalignant. Oral pathologists use the term epithelial dysplasia to indicate microscopic features in a biopsy specimen that are associated with a risk of malignant change and then assign a grade of severity. There is good correlation between higher grades of dysplasia and increasing risk of cancer but less so with the lower grades. The clinical appearances manifested by oral epithelial dysplasia and early oral cancer include leukoplakia, erythroplakia, and speckled leukoplakia. This paper discusses and illustrates these clinical lesions, their associated risk factors, their relationship to epithelial dysplasia, and the associated risk of evolution into oral cancer.
Topics: Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Epithelium; Erythroplasia; Humans; Leukoplakia, Oral; Mouth Mucosa; Mouth Neoplasms; Precancerous Conditions; Risk Factors; Sunlight
PubMed: 11577670
DOI: No ID Found -
Oral Oncology May 2019This communication presents a discussion of patient risk factors and outcomes for potentially malignant and malignant lesions in contrast to lesion assessment and lesion...
This communication presents a discussion of patient risk factors and outcomes for potentially malignant and malignant lesions in contrast to lesion assessment and lesion management. The shift in consideration may have implications for research and clinical intervention. This compact review discusses several local and systemic components that contribute to the development of malignant changes and discusses whether patients instead of lesions should be defined as having a potentially premalignant condition.
Topics: Cell Transformation, Neoplastic; Humans; Mouth Neoplasms; Precancerous Conditions; Risk Assessment; Risk Factors
PubMed: 31010624
DOI: 10.1016/j.oraloncology.2019.03.009 -
The American Journal of Gastroenterology May 1996The definition of a "premalignant" lesion is discussed, together with its relationship to dysplastic change. The definition and description of dysplasia are given.... (Review)
Review
The definition of a "premalignant" lesion is discussed, together with its relationship to dysplastic change. The definition and description of dysplasia are given. Systems for grading dysplasia are set out, and the clinical implications of these changes are discussed. Although the "dysplasia terminology" in current use remains the gold standard for clinical practice, a series of more recent developments, including the discovery of flat and depressed adenomas, the possibility of de novo carcinoma throughout the gastrointestinal tract, as well as advances in molecular biology, raise the question of whether this terminology will be adequate in future. Other terminologies exist that provide an alternative viewpoint, but none is satisfactory.
Topics: Gastrointestinal Neoplasms; Humans; Neoplasm Invasiveness; Precancerous Conditions; Terminology as Topic
PubMed: 8633573
DOI: No ID Found -
Otolaryngologic Clinics of North America Apr 2023There have been many advancements in the clinical and histologic diagnosis of laryngeal dysplasia (LD), but diagnosis still necessitates invasive histologic evaluation.... (Review)
Review
There have been many advancements in the clinical and histologic diagnosis of laryngeal dysplasia (LD), but diagnosis still necessitates invasive histologic evaluation. Furthermore, despite improved histologic identification of dysplastic lesions, the exact details of pathophysiologic progression and the risk of malignant transformation is still uncertain. These unknowns create a barrier to establishing an ideal grading and classification system, which prevents the establishment of a precise and consistent treatment paradigm. Identifying these gaps in knowledge serves to highlight where further studies are warranted, ideally focusing on a better understanding of the biological behavior of LD. This would ultimately allow for the creation of a reliable grading and classification system and for the formalization of management and treatment guidelines for LD.
Topics: Humans; Laryngeal Neoplasms; Larynx; Precancerous Conditions; Vocal Cords
PubMed: 37030937
DOI: 10.1016/j.otc.2023.01.001 -
Advances in Anatomic Pathology May 2002There is currently great interest in the detection and characterization of putative precursor breast cancer lesions because of the possibility of chemoprevention.... (Review)
Review
There is currently great interest in the detection and characterization of putative precursor breast cancer lesions because of the possibility of chemoprevention. Knowledge of the biologic features of premalignant lesions, although limited, is rapidly evolving. Premalignant breast lesions have been examined for the presence of genetic alterations and for the expression of biomarkers such as the estrogen receptor (ER), Ki67, p53, and HER2/neu. Data obtained from genetic studies of precursor breast lesions clearly support the contention that genetic alterations begin quite early in selected subsets of histologically benign lesions. Although the results of biomarker expression profiles have been contradictory, most studies agree that precursor lesions significantly overexpress ER and that progressive alterations in ER expression accompany the transition of normal cells to hyperplastic lesions and carcinoma in situ. So far, the collected evidence indicates that precursor lesions in the breast demonstrate biomarker expression profiles and genetic abnormalities that are distinct from those of terminal ductal lobular units but share some of these features with invasive tumors. Future research in this field is urgently needed to identify specific biomarkers of prognostic and predictive value, which can help not only in the selection of patients for chemopreventive therapy but in monitoring the progression of high-risk lesions.
Topics: Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma in Situ; Genetic Markers; Hyperplasia; Precancerous Conditions
PubMed: 11981114
DOI: 10.1097/00125480-200205000-00002 -
Journal of Cellular Biochemistry.... 1993Patients with premalignant and malignant lesions of the upper aerodigestive tract have historically been the focus of chemoprevention trials within the United States.... (Review)
Review
Patients with premalignant and malignant lesions of the upper aerodigestive tract have historically been the focus of chemoprevention trials within the United States. Experience with this population has formed the basis for trials involving other environmentally induced cancers such as lung and bladder. Given that head and neck cancer patients are at risk for second primary malignancies, prevention strategies can be directed towards decreasing mortality from these metachronous neoplasias. Validity of these strategies, including risk determination, intermediate endpoints, and preventive efficacy of single and combination agents, can be determined. Current limitations in chemoprevention trials involving these patients relate to the sporadic nature of the disease. In fact, the prevalence of oral premalignancy within the United States has not been clearly defined. Individual physician experience with this disease process is limited. Organizational efforts should therefore be directed towards facilitating clinical trials involving dentists, oral surgeons, head and neck surgeons, and other primary health care providers in the community. Risk factors which identify clinically defined normal or premalignant tissue at risk for malignant progression need to be better defined.
Topics: Anticarcinogenic Agents; Biomarkers, Tumor; Digestive System Neoplasms; Head and Neck Neoplasms; Humans; Precancerous Conditions; Respiratory Tract Neoplasms
PubMed: 8412190
DOI: 10.1002/jcb.240531004