Proteomic applications for the early detection of cancer

The ability of physicians to effectively treat and cure cancer is directly dependent on their ability to detect cancers at their earliest stages. Proteomic analyses of early-stage cancers have provided new insights into the changes that occur in the early phases of tumorigenesis and represent a new resource of candidate biomarkers for early-stage disease. Studies that profile proteomic patterns in body fluids also present new opportunities for the development of novel, highly sensitive diagnostic tools for the early detection of cancer.     

The current status of early detection and screening for colorectal cancer

There are several approaches to the early detection of colorectal cancer that currently are in use in various segments of the health care system. Herein, the status of cancer control research regarding symptom and risk factor assessment, sigmoidoscopy and colonoscopy, double contrast barium enema, and fecal occult blood testing is reviewed. In addition to the different technologies of early cancer detection, there are different models of disease control intervention. These include the routine clinical activities of primary care providers as well as programmatic screening of mass populations. The currently available techniques for early colorectal cancer detection appear better suited for existing patient care settings than for programs outside the direct supervision and follow-up of the health professional.     

Screening and early cancer detection

NCI is the primary research institution that has funded most of the research to establish evidence of benefit from mass cancer screening. A study of prostate, lung, and colorectal cancer is presently being planned. These trials are large, expensive, and require 10 to 15 years or longer to complete. RCST trials are only feasible in the three or four most common sites. While developing better evidence, NCI suggests the Working Guidelines for the Early Detection of Cancer in seven sites where direct and/or indirect evidence suggests benefit. The potential for early cancer detection to contribute to a decrease in cancer mortality is great. However, unless early detection is applied by the public and by physicians, it is useless. It is hoped that this chapter has been helpful to physicians and oncologists in judging these matters and applying the benefits to patients.     

The state of molecular biomarkers for the early detection of lung cancer

Using biomarkers to select the most at-risk population, to detect the disease while measurable and yet not clinically apparent has been the goal of many investigations. Recent advances in molecular strategies and analytic platforms, including genomics, epigenomics, proteomics, and metabolomics, have identified increasing numbers of potential biomarkers in the blood, urine, exhaled breath condensate, bronchial specimens, saliva, and sputum, but none have yet moved to the clinical setting. Therefore, there is a recognized gap between the promise and the product delivery in the cancer biomarker field. In this review, we define clinical contexts where risk and diagnostic biomarkers may have use in the management of lung cancer, identify the most relevant candidate biomarkers of early detection, provide their state of development, and finally discuss critical aspects of study design in molecular biomarkers for early detection of lung cancer. Cancer Prev Res; 5(8); 992-1006. ?2012 AACR.     

Efforts for early detection of lung cancer

The 3rd survey of "The Lung Cancer Early Detection Project" inaugurated in 1972, was conducted by Naruke team during the period from 1978 to 1980 on 1, 632, 157 test subjects collected from 60 institutions throughout Japan. Cases of detected lung cancer were classified in two groups as Prevalence case and Incidence case and discussed in the report. As the result, X-ray examination was effective to detect early peripheral lung cancer, and for high risk group X-ray examination combined with sputum cytology test indicated the highest detection rate for early hilar lung cancer. Our recent directions for the nation-wide mass screening of lung cancer consist of four methods: 1. Utilization of local self-governmental mass screening. 2. Mass screening conducted by general practitioners at local clinics. 3. Active cooperation of general practitioners with local self-government. 4. Public participation in the Lung Project. We should continue our efforts to solve these problems.     

Prevention and early detection of cancer

The axiom that prevention is better than cure is especially true for a serious disease such as cancer for which therapy is expensive and seldom fully effective. However, it is only for some cancers that the major determinants are known and for which primary prevention programs are likely to result in substantial reduction in incidence. Past efforts at primary prevention have not been very successful where avoidance of cancer determinants involves changing pleasurable personal habits or has major economic effects. Control of the disease is now largely based on therapy. Because successful therapy is influenced by the stage of the disease at diagnosis there is increasing interest in early detection through the application of various screening techniques. Only some of these have been demonstrably effective in reducing cancer mortality. The introduction of any mass screening program should be based on an assessment of its costs, risks, and effectiveness in reducing mortality from the disease.     

Novel strategies for the early detection and prevention of lung cancer

Lung cancer is the leading cause of cancer death in the United States. Despite evidence of molecular abnormalities in biological specimens, progress in this disease is hampered by the lack of diagnostic markers useful for clinical practice. The majority of patients with lung cancer are still diagnosed at an advanced stage, when prognosis is poor. This article reviews new strategies being studied for the early detection of lung cancer. These strategies involve new methods of imaging (including low-dose computed tomography [CT] scanning), DNA analysis, and proteomic-based techniques. These strategies have not only improved our understanding of lung cancer but show promise in offering better survival to patients with this deadly disease. Of paramount importance in the search for methods of early detection is the need for the identification of the ideal population to screen, a multidisciplinary approach, and validation of promising techniques.     

The importance of early symptom recognition in the context of early detection and cancer survival

Since there is evidence that stage is an important prognostic factor in cancer, interventions aimed at ‘down-staging’ are part of a comprehensive cancer control approach. Besides organised screening programmes, raising awareness of detectable signs and symptoms is recommended.A precise definition of early cancer signs and symptoms, however, is lacking and there has also been no systematic review regarding the impact of awareness raising interventions on cancer outcomes.We reviewed the scientific medical literature to assess the consistency and availability of a definition for early cancer symptoms as well as to assess the impact of early cancer diagnosis on survival. Although early diagnosis is an important factor for cancer survival, other considerations such as the cancer profile of a country, the characteristics of cancer types and the availability of devices for diagnosis should be taken into account in promoting early cancer detection. There is a clear need for research to categorise cancer types according to early symptoms in order to increase comparability of studies in this field and to provide guidance for health personnel in primary care settings in low income regions.     

Treatment options for early breast cancer in elderly women

In clinical practice, approximately 50% of new cases of breast cancer occur in women over the age of 65 years, although very few elderly women have been enrolled in the numerous randomized trials conducted so far. Notwithstanding less aggressive biologic features compared with younger patients, breast cancer impacts on mortality of elderly women, especially if not adequately treated. As confirmed by meta-analyses, hormonal therapy is the most effective adjuvant measure for patients with localized disease, whereas the decrease in the benefit of cytotoxic treatment with increased risk of toxicity make the decision on when and how to administer it a major challenge for the medical oncologist. Careful evaluation of biological prognostic factors, performance status and geriatric parameters, such as functional independence, comorbidities and cognitive function of the patient, along with determination of her life expectancy and preferences, represent the relevant information on which the oncologist should ground their decision for integrated treatment with conservative surgery, radiotherapy and hormonochemotherapy in otherwise healthy women, or attenuated or palliative measures for the frail patients, in order to maximize the balance of benefits and toxicities. The aims of this review are to summarize the most relevant concepts for decision making in the clinical practice and discuss the results of recent research concerning the additional needs of elderly women with early breast cancer.     

开展早癌筛查研究面临的问题

陈世耀,医学博士,主任医师,博士研究生导师。现任复旦大学中山医院内科教研室主任/临床技能中心主任、消化科/内镜中心副主任、复旦大学循证医学中心副主任。兼任中华医学会临床流行病学和循证医学分会主任委员,中华医学会消化分会临床流行病协作组组长,消化分会幽门螺杆菌学组成员,消化内镜分会食管胃静脉曲张学组成员,上海医学会食管胃静脉曲张治疗分会主任委员、内科分会委员、胃肠动力学组成员。长期从事临床一线医疗和教学工作,在临床医疗和教学实践中贯穿循证医学理念。专业特长：胃肠病、肝病诊断与治疗;消化内镜检查和治疗,包括胃镜、肠镜、ERCP、超声内镜检查及相关治疗;临床科研设计、测量和评价。科研方向：肝硬化门脉高压食管胃静脉曲张出血的综合治疗;食管癌、胃癌的早期发现与内镜下治疗;胃肠动力疾病/酸相关疾病/胃肠黏膜损害;拓展消化内镜的临床应用;循证医学在消化病诊断与治疗中的应用。先后承担科技部、市科委等科研课题,获国家科技进步奖二等奖、上海医学科技一等奖等成果和荣誉,发表学术论文160余篇。     

Serum proteomic pattern analysis for early cancer detection

The ability of physicians to effectively treat and cure cancer is directly dependent on their ability to detect cancers at their early stages. The early detection of cancer has the potential to dramatically reduce mortality. Recently, the use of mass spectrometry to develop profiles of patient serum proteins has been reported as a promising method to achieve this goal. In this paper, we analyzed the ovarian cancer and prostate cancer data sets using support vector machine (SVM) to detect cancer at the early stages based on serum proteomic pattern. The results showed that SVM, in general, performed well on these two data sets, as measured by sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. Linear kernel worked the best on ovarian cancer data with a sensitivity of 0.99 and an accuracy of 0.97, while polynomial kernel worked the best on prostate cancer data with a sensitivity of 0.79 and an accuracy of 0.82. When redial kernel was applied to either of the two data sets, all the samples were predicted as cancer samples, with a sensitivity of 1 and a specificity of 0. Furthermore, feature selection did not improve SVM performance.     

Biomarkers for early detection of colon cancer.

There is an increasing demand for biomarkers in colon cancer for risk assessment, early detection, prognosis, and surrogate end points. A number of biomarkers have been identified for early detection of colon cancer, although the risk factors have not been identified extensively. The major advances in understanding colorectal cancer include the identification and the involvement of APC, p53, and Ki-ras in the development and progression of the disease, the identification of the aberrant crypt foci as an early preinvasive lesion, and its relation to the development of cancer. Detecting malignant neoplasms in the early stages offers clinical advantages; therefore, the National Cancer Institute has established an Early Detection Research NETWORK: The emphasis of the network is on translational research and collaboration among scientists.     

Management of early breast cancer in the elderly

Breast cancer is the most common malignancy in women with an age related increase in incidence ranging from 1 in 50 at age 50 to 1 in 10 at age 80. This is particularly significant in view of the changing demographics in the western population, characterised by an aging population and increased life expectancy. However in spite of favourable prognostic factors and less aggressive biological behaviour, elderly breast cancer patients receive less aggressive treatment when compared with their younger counterparts. Appropriate treatment should be offered depending on physiological reserve and comorbidities. Primary endocrine treatment has been shown to be associated with significant morbidity in terms of disease progression. Prompt surgery and adjuvant treatment can decrease relapse and improve survival. Radiation therapy is shown to decrease local relapse and chemotherapy may have a role in a select group of patients with adverse prognostic factors. With incidence of breast cancer bound to increase in the elderly population, it is essential to establish optimum therapy in this cohort of patients as studies reveal good outcome from standard treatment.     

Methylation-based biomarkers for early detection of urological cancer

Genitourinary (prostate, bladder, and kidney) cancers together comprise the most common type of human neoplasms. As a common feature to these types of malignancy, the disease is frequently asymptomatic at its earlier stages, when curative treatment is most likely to be successful. Moreover, available tests for genitourinary cancer screening (mostly directed to prostate cancer) are characterized by variable (usually low) sensitivity and specificity, preventing a consensual support for their routine use by the medical community. Thus, the timely and accurate detection of GU cancer remains a significant clinical challenge. Over the last decade, a new generation of cancer biomarkers, based on the characterization of the methylome, has emerged and has showed promise in the detection of several common malignant tumors. The investigation of novel genitourinary cancer methylation-based markers constitutes an attractive and fast-growing research field, and several studies reported on the feasibility of examining these markers in body fluids (urine and blood) for early, noninvasive cancer detection. Importantly, the use of quantitative, high-throughput techniques enables relatively easy and reproducible detection of hypermethylation at multiple gene loci in a single test, thus facilitating its translation to the clinics. Although available data is still insufficient to support the clinical implementation of these markers at the present time, further developments in methylation analysis are likely to provide valuable tests for genitourinary cancer screening and management.