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Science (New York, N.Y.) Apr 2020Metabolic reprogramming is a hallmark of malignancy. As our understanding of the complexity of tumor biology increases, so does our appreciation of the complexity of... (Review)
Review
Metabolic reprogramming is a hallmark of malignancy. As our understanding of the complexity of tumor biology increases, so does our appreciation of the complexity of tumor metabolism. Metabolic heterogeneity among human tumors poses a challenge to developing therapies that exploit metabolic vulnerabilities. Recent work also demonstrates that the metabolic properties and preferences of a tumor change during cancer progression. This produces distinct sets of vulnerabilities between primary tumors and metastatic cancer, even in the same patient or experimental model. We review emerging concepts about metabolic reprogramming in cancer, with particular attention on why metabolic properties evolve during cancer progression and how this information might be used to develop better therapeutic strategies.
Topics: Animals; Disease Progression; Humans; Mice; Molecular Targeted Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Precancerous Conditions
PubMed: 32273439
DOI: 10.1126/science.aaw5473 -
Journal of Dental Research Nov 2021Oral cancer is a major public health problem, and there is an increasing trend for oral cancer to affect young men and women. Public awareness is poor, and many patients... (Review)
Review
Oral cancer is a major public health problem, and there is an increasing trend for oral cancer to affect young men and women. Public awareness is poor, and many patients present with late-stage disease, contributing to high mortality. Oral cancer is often preceded by a clinical premalignant phase accessible to visual inspection, and thus there are opportunities for earlier detection and to reduce morbidity and mortality. Screening asymptomatic individuals by systematic visual oral examinations to detect the disease has been shown to be feasible. A positive screen includes both oral cancer and oral potentially malignant disorders. We review key screening studies undertaken, including 1 randomized clinical trial. Screening of high-risk groups is cost-effective. Strengths and weaknesses of oral cancer screening studies are presented to help guide new research in primary care settings and invigorated by the prospect of using emerging new technologies that may help to improve discriminatory accuracy of case detection. Most national organizations, including the US Preventive Services Task Force, have so far not recommended population-based screening due a lack of sufficient evidence that screening leads to a reduction in oral cancer mortality. Where health care resources are high, opportunistic screening in dental practices is recommended, although the paucity of research in primary care is alarming. The results of surveys suggest that dentists do perform oral cancer screenings, but there is only weak evidence that screening in dental practices leads to downstaging of disease. Where health care resources are low, the feasibility of using primary health care workers for oral cancer screening has been tested, and measures indicate good outcomes. Most studies reported in the literature are based on 1 round of screening, whereas screening should be a continuous process. This review identifies a huge potential for new research directions on screening for oral cancer.
Topics: Early Detection of Cancer; Female; Humans; Male; Mass Screening; Mouth Neoplasms; Precancerous Conditions; Primary Health Care; Randomized Controlled Trials as Topic
PubMed: 34036828
DOI: 10.1177/00220345211014795 -
Science (New York, N.Y.) Nov 2019As people age, their tissues accumulate an increasing number of somatic mutations. Although most of these mutations are of little or no functional consequence, a... (Review)
Review
As people age, their tissues accumulate an increasing number of somatic mutations. Although most of these mutations are of little or no functional consequence, a mutation may arise that confers a fitness advantage on a cell. When this process happens in the hematopoietic system, a substantial proportion of circulating blood cells may derive from a single mutated stem cell. This outgrowth, called "clonal hematopoiesis," is highly prevalent in the elderly population. Here we discuss recent advances in our knowledge of clonal hematopoiesis, its relationship to malignancies, its link to nonmalignant diseases of aging, and its potential impact on immune function. Clonal hematopoiesis provides a glimpse into the process of mutation and selection that likely occurs in all somatic tissues.
Topics: Aged; Aging; Animals; Cardiovascular Diseases; Clonal Evolution; Clone Cells; Hematologic Neoplasms; Hematopoiesis; Hematopoietic Stem Cells; Humans; Mutation; Precancerous Conditions
PubMed: 31672865
DOI: 10.1126/science.aan4673 -
Blood Oct 2020The nucleophosmin (NPM1) gene encodes for a multifunctional protein with prominent nucleolar localization that shuttles between nucleus and cytoplasm. NPM1 mutations... (Review)
Review
The nucleophosmin (NPM1) gene encodes for a multifunctional protein with prominent nucleolar localization that shuttles between nucleus and cytoplasm. NPM1 mutations represent the most common genetic lesion in adult acute myeloid leukemia (AML; about one third of cases), and they act deterministically to cause the aberrant cytoplasmic delocalization of NPM1 mutants. Because of its unique features, NPM1-mutated AML is recognized as a distinct entity in the 2017 World Health Organization (WHO) classification of hematopoietic neoplasms. Here, we focus on recently identified functions of wild-type NPM1 in the nucleolus and address new biological and clinical issues related to NPM1-mutated AML. The relevance of the cooperation between NPM1 and other mutations in driving AML with different outcomes is presented. We also discuss the importance of eradicating NPM1-mutated clones to achieve AML cure and the impact of preleukemic clonal hematopoiesis persistence in predisposing to second AML. The contribution of HOX genes' expression to the development of NPM1-mutated AML is also highlighted. Clinically, yet unsolved diagnostic issues in the 2017 WHO classification of myeloid neoplasms and the importance of NPM1 mutations in defining the framework of European LeukemiaNet genetic-based risk stratification are discussed. Finally, we address the value and limits of NPM1-based measurable residual disease assessment for treatment guidance and present the results of promising preclinical studies with XPO1 and menin-MLL inhibitors.
Topics: Animals; Cell Transformation, Neoplastic; Clonal Hematopoiesis; Disease Management; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Leukemia, Myeloid, Acute; Mutation; Nuclear Proteins; Nucleophosmin; Precancerous Conditions; Prognosis; Translational Research, Biomedical
PubMed: 32609823
DOI: 10.1182/blood.2019004226 -
Digestive Surgery 2020The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological... (Review)
Review
BACKGROUND
The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological entities with different potential for malignant transformation. The clinician must balance his or her practice between the risk of surgical overtreatment and the error of keeping a malignant lesion under surveillance.
METHODS
We review and discuss the clinical management of PCNs. Specifically, we analyze the main features of PCNs from the surgeon's point of view, as they present in the outpatient clinic. We also review the different consensus guidelines, address recent controversies in the literature, and present the current clinical practice at 4 different European Centers for pancreatic surgery.
RESULTS
The main features of PCNs were analyzed from the surgeon's point of view as they present in the outpatient clinic. All aspects of surgical management were discussed, from indications for surgery to intraoperative management and surveillance strategies.
CONCLUSIONS
Management of PCNs requires a selective approach with the aim of minimizing clinically relevant diagnostic mistakes. Through the evaluation of clinical and radiological features of a PCN, the surgeon can elaborate on a diagnostic hypothesis and assess malignancy risk, but the final decision should be tailored to the individual patient's need.
Topics: Humans; Pancreas; Pancreatectomy; Pancreatic Cyst; Pancreatic Neoplasms; Practice Guidelines as Topic; Precancerous Conditions
PubMed: 30636253
DOI: 10.1159/000496509 -
Virchows Archiv : An International... Jul 2023The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have... (Review)
Review
The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB). In case of B3 lesion diagnosis on CNB, OE was recommended in ADH and PT, whereas in the other B3 lesions, vacuum-assisted excision was considered an equivalent alternative to OE. In ADH, most panelists (76%) recommended an open excision (OE) after diagnosis on VAB, whereas observation after a complete VAB-removal on imaging was accepted by 34%. In LN, the majority of the panel (90%) preferred observation following complete VAB-removal. Results were similar in RS (82%), PL (100%), and FEA (100%). In benign PT, a slim majority (55%) also recommended an observation after a complete VAB-removal. VAB with subsequent active surveillance can replace an open surgical intervention for most B3 lesions (RS, FEA, PL, PT, and LN). Compared to previous recommendations, there is an increasing trend to a de-escalating strategy in classical LN. Due to the higher risk of upgrade into malignancy, OE remains the preferred approach after the diagnosis of ADH.
Topics: Humans; Female; Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Mammography; Biopsy, Large-Core Needle; Precancerous Conditions; Phyllodes Tumor; Retrospective Studies
PubMed: 37330436
DOI: 10.1007/s00428-023-03566-x -
Biomedicine & Pharmacotherapy =... Feb 2022Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years... (Review)
Review
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years of precancerous lesions of gastric cancer (PLGC) stages before progressing to gastric malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven effective in treating PLGC. Classical TCM formulas and chemical components isolated from some Chinese herbal medicines have been administered to treat PLGC, and the main advantage is their comprehensive intervention with multiple approaches and multiple targets. In this review, we focus on recent studies using TCM treatment for PLGC, including clinical observations and experimental research, with a focus on targets and mechanisms of drugs. This review provides some ideas and a theoretical basis for applying TCM to treat PLGC and prevent GC.
Topics: Drugs, Chinese Herbal; Gastric Mucosa; Humans; Medicine, Chinese Traditional; Precancerous Conditions; Stomach Neoplasms
PubMed: 34929576
DOI: 10.1016/j.biopha.2021.112542 -
Gastroenterology Apr 2023Gastric cancer (GC) is a leading cause of global mortality but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology,... (Review)
Review
Gastric cancer (GC) is a leading cause of global mortality but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology, critically appraise strategies of prevention and disease attenuation, and assess how these strategies could be applied to improve outcomes from GC in a world of variable risk and disease burden. Strategies of primary prevention focus on improving the detection and eradication of the main environmental risk factor, Helicobacter pylori. In certain countries of high incidence, endoscopic or radiographic screening of the asymptomatic general population has been adopted as a means of secondary prevention. By contrast, identification and targeted surveillance of individuals with precancerous lesions (such as intestinal metaplasia) is being increasingly embraced in nations of low incidence. This review also highlights existing knowledge gaps in GC prevention as well as the role of emerging technologies for early detection and risk stratification.
Topics: Humans; Stomach Neoplasms; Helicobacter Infections; Precancerous Conditions; Endoscopy; Incidence; Helicobacter pylori; Metaplasia; Gastric Mucosa; Risk Factors
PubMed: 36706842
DOI: 10.1053/j.gastro.2023.01.018 -
Actas Dermo-sifiliograficas Sep 2020Porokeratosis comprises a group of heterogeneous and uncommon acquired or congenital skin diseases of unknown origin characterized by a keratinization disorder resulting... (Review)
Review
Porokeratosis comprises a group of heterogeneous and uncommon acquired or congenital skin diseases of unknown origin characterized by a keratinization disorder resulting from abnormal clonal expansion of keratinocytes. Numerous genetic mutations are thought to be involved. These conditions are characterized histologically by the presence of a cornoid lamella. Clinical manifestations are variable, with localized, disseminated, and even eruptive forms. Porokeratosis has been associated with immunosuppression, ultraviolet radiation, and systemic, infectious, and neoplastic diseases. Many authors consider it to be a premalignant condition because of the potential for malignant transformation to squamous cell or basal cell carcinoma. Therefore, long-term follow-up is a key component of treatment, which is usually complex and often unsatisfactory. We review the latest advances in our understanding of the pathogenesis, diagnosis, and treatment and propose a treatment algorithm.
Topics: Cell Transformation, Neoplastic; Humans; Porokeratosis; Precancerous Conditions; Skin Neoplasms; Ultraviolet Rays
PubMed: 32401728
DOI: 10.1016/j.ad.2020.03.005 -
World Journal of Gastroenterology May 2020In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway.... (Review)
Review
In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway. Colorectal serrated polyps are histopathologically classified into hyperplastic polyps (HPs), sessile serrated lesions, and traditional serrated adenomas; in the serrated neoplasia pathway, the latter two are considered to be premalignant. In western countries, all colorectal polyps, including serrated polyps, apart from diminutive rectosigmoid HPs are removed. However, in Asian countries, the treatment strategy for colorectal serrated polyps has remained unestablished. Therefore, in this review, we described the clinicopathological features of colorectal serrated polyps and proposed to remove HPs and sessile serrated lesions ≥ 6 mm in size, and traditional serrated adenomas of any size.
Topics: Adenoma; Clinical Decision-Making; Colectomy; Colon; Colonic Polyps; Colorectal Neoplasms; Humans; Hyperplasia; Intestinal Mucosa; Narrow Band Imaging; Practice Guidelines as Topic; Precancerous Conditions; Proctectomy; Rectum; Treatment Outcome
PubMed: 32476792
DOI: 10.3748/wjg.v26.i19.2276