Up close and personal: molecular diagnostics in oncology.

The almost overwhelming volume of information and new technological developments that has demanded so much of our scientific attention over the last decade will shortly revolutionize clinical diagnostics. Some of these developments are already affecting the working lives of scientists and clinicians alike, but will eventually require a greater understanding and acceptance from a much wider audience. Therefore it is important in our current scientific endeavor and commercial enthusiasm for molecular diagnostics that we maintain some awareness of the significant obstacles that must be overcome if we are to see an appropriate, timely and widespread adoption of molecular diagnostic testing in oncology. This article presents a brief commentary on the current state of the art in molecular diagnostics in oncology and how this relates to a more personalized approach to treatment.     

Recent advances in nanooncology

Nanobiotechnology is playing an important role in advances in oncology and currently nanooncology is the most important chapter of nanomedicine. Nanobiotechnologies have refined molecular diagnostics and enabled early detection of tumors and discovery of biomarkers of cancer. Various nanoparticles are the basis of diagnostic assays for cancer as well as contrast materials for MRI. Nanobiotechnology is facilitating the discovery and development of drugs for cancer. Several nanobiotechnologies, mostly based on nanoparticles, have been described to facilitate drug delivery in cancer, which is important for optimizing the effect of drugs and reducing toxic side effects. Nanoparticles for targeted drug delivery in cancer enable combination of diagnostics and therapeutics and act as adjuncts to hyperthermia and photodynamic therapy. Several applications of nanobiotechnology in cancer surgery include use of nanoparticles to visualize tumor during surgery as aid to proper removal, and nanorobotics for remotely controlled diagnostics combined with therapeutics. Selected new developments in nanooncology have been highlighted in this review and these point to an important role in development of personalized oncology.     

Scientific Advances in Thoracic Oncology 2016

Lung cancer care is rapidly changing with advances in genomic testing, the development of next-generation targeted kinase inhibitors, and the continued broad study of immunotherapy in new settings and potential combinations. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in thoracic cancer and care provide focused updates across multiple areas, including prevention and early detection, molecular diagnostics, pathology and staging, surgery, adjuvant therapy, radiotherapy, molecular targeted therapy, and immunotherapy for NSCLC, SCLC, and mesothelioma. Quality and value of care and perspectives on the future of lung cancer research and treatment have also been included in this concise review.     

Molecular mechanisms of head and neck cancer

Despite advances in understanding the underlying genetics, squamous cell carcinoma of the head and neck (SCCHN) remains a major health risk and one of the leading causes of mortality in the world. Current standards of treatment have significantly improved long-term survival rates of patients, but second tumors and metastases still remain the most frequent cause of high mortality in SCCHN patients. A better understanding of the underlying genetic mechanisms of SCCHN tumorigenesis will help in developing better diagnostics and, hence, better cures. In this article we will briefly outline the current state of diagnostics and treatment and our understanding of the molecular causes of SCCHN.     

New developments in the diagnosis and treatment of thyroid cancer

Answer questions and earn CME/CNE Thyroid cancer exists in several forms. Differentiated thyroid cancers include those with papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from those of differentiated thyroid tumors. Genetic testing and newer adjuvant therapies have changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, workup, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. CA Cancer J Clin 2013;63:373‐394. ^©2013 American Cancer Society, Inc.     

Molecular mechanisms of head and neck cancer

Despite advances in understanding the underlying genetics, squamous cell carcinoma of the head and neck (SCCHN) remains a major health risk and one of the leading causes of mortality in the world. Current standards of treatment have significantly improved long-term survival rates of patients, but second tumors and metastases still remain the most frequent cause of high mortality in SCCHN patients. A better understanding of the underlying genetic mechanisms of SCCHN tumorigenesis will help in developing better diagnostics and, hence, better cures. In this article we will briefly outline the current state of diagnostics and treatment and our understanding of the molecular causes of SCCHN.     

Predictive biomarkers: a paradigm shift towards personalized cancer medicine

Advances in our understanding of the intricate molecular mechanisms for transformation of a normal cell to a cancer cell, and the aberrant control of complementary pathways, have presented a much more complex set of challenges for the diagnostic and therapeutic disciplines than originally appreciated. The oncology field has entered an era of personalized medicine where treatment selection for each cancer patient is becoming individualized or customized. This advance reflects the molecular and genetic composition of the tumors and progress in biomarker technology, which allow us to align the most appropriate treatment according to the patient's disease. There is a worldwide acceptance that advances in our ability to identify predictive biomarkers and provide them as companion diagnostics for stratifying and subgrouping patients represents the next leap forward in improving the quality of clinical care in oncology. As such, we are progressing from a population-based empirical 'one drug fits all' treatment model, to a focused personalized approach where rational companion diagnostic tests support the drug's clinical utility by identifying the most responsive patient subgroup.     

Gene therapy for lung cancer

The advances that have been made over the past decade in the field of gene transfer as well as in the fields of immunology and the molecular biology of tumorigenesis have brought to reality the possibility of using gene transfer as an anti-cancer treatment modality. The published results of clinical trials using this approach to date have been very limited, and a considerable amount of work still needs to be done in order to make this an effective treatment modality. However the developments that have occurred in the past several years indicate that this modality will become efficacious in the foreseeable future.     

Comprehensive Gene Mutation Profiling of Breast Tumors: Is It Ready for Prime Time Use?

Recent advances in molecular biology have led to unprecedented innovations in diagnosis and treatment of breast cancer. The advent of genomics has revolutionized our understanding of breast cancer. It is no longer considered a single disease but several different biologically and molecularly distinct entities. This research has led to commercially available polymerase chain reaction (PCR)-, microarray-, and next generation sequencing (NGS)-based tests which have changed the way oncologists estimate recurrence risk in early stage breast cancer patients. The genomics era has altered the clinicopathologic paradigm of selecting patients for adjuvant cytotoxic chemotherapy. Numerous well designed prospective studies are underway that may establish these molecular assays as basic elements of standard clinical practice in breast cancer diagnostics and therapeutics. In this article, we review the robustnesses and constraints of currently available breast cancer-specific molecular tests and their clinical ramifications.     

Molecular diagnostics and biomarkers in cholangiocarcinoma

Regardless of anatomic origin, cholangiocarcinoma is generally an aggressive malignancy with a relatively high case fatality. Surgical resection with curative intent remains the best opportunity to achieve meaningful long-term survival. Most patients present, however, with advanced disease and less than 20% of patients are candidates for surgical resection. Unfortunately, even patients who undergo resection have a 5-year survival that ranges from 20 to 40%. Biomarkers are indicators of normal, pathologic, or biologic responses to an intervention and can range from a characteristic (i.e., blood pressure reading which can detect hypertension) to specific genetic mutations or proteins (i.e., carcinoembryonic antigen level). Novel biomarkers and improved molecular diagnostics represent an attractive opportunity to improve detection as well as to identify novel therapeutic targets for patients with cholangiocarcinoma. We herein review the latest advances in molecular diagnostics and biomarkers related to the early detection and treatment of patients with cholangiocarcinoma.     

Immuno-PET: a navigator in monoclonal antibody development and applications

Monoclonal antibodies (mAbs) have been approved for use as diagnostics and therapeutics in a broad range of medical indications, but especially in oncology. In addition, hundreds of new mAbs, engineered mAb fragments, and nontraditional antibody-like scaffolds directed against either validated or novel tumor targets are under development. Immuno-positron emission tomography (PET), the tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and to guide mAb-based therapy. In this review, recent technical advances leading to a jump ahead in mAb imaging are discussed. The availability of proper positron emitters, sophisticated radiochemistry, and advanced PET and PET-computed tomography scanners is crucial in these developments. Immuno-PET might play an important future role in cancer staging, in the improvement and tailoring of therapy with existing mAbs, and in the efficient development of novel mAbs. An overview of the preclinical and first clinical immuno-PET studies is provided.     

Functional imaging in clinical oncology: magnetic resonance imaging- and computerised tomography-based techniques

Over recent years, advances in cellular biology, molecular biology and genetics have led to a leap forward in our understanding of the biological basis of cancer. Some of these developments have revealed processes and targets that can be visualised and measured by new functional imaging techniques. The resulting images have the potential to improve cancer staging, prognosis and risk assessment, guide radiotherapy planning, direct treatment schedules, improve response assessment and provide new end points for clinical trials. In this review, we have outlined the magnetic resonance imaging- and computerised tomography-based functional techniques and provide evidence for their use.     

肾细胞癌相关分子标志物研究现状及进展

近年,有关肾细胞癌病理学、遗传性及分子生物学方面的研究取得显著进展,这对提高肾细胞癌早期诊断、预后判断及治疗水平有重要意义。目前研究的多个肾细胞癌相关分子标志物(如CAⅨ、B7-H1等)对于肾细胞癌患者的预后判断有一定意义。本文总结了近年来与肾细胞癌患者有关的肿瘤标志物,分析其与肾细胞癌的诊断、治疗和预后方面关系。     

Soft-tissue sarcomas: an update.

Despite their relative infrequency (which is often used as an excuse for poor treatment), soft-tissue sarcomas have been the focus of considerable interest and advances in recent years, mainly because of molecular genetic developments as well as evolution in their histological classification. In parallel, however, there remains no clear consensus regarding either the ideal biopsy technique (in this era of increasing outpatient management) or the best means of prognostication (particularly by histological grading). This review aims to discuss some of these recent developments and co-existent controversies. Aside from the understandable pursuit of modern biotechnological innovations, it seems that the most important goal remains the need to achieve more consistent primary surgical management of these tumours, preferably in specialist centres.     

Wnt信号通路与肿瘤及肿瘤靶点治疗研究新进展

Wnt信号传导通路与肿瘤的关系是近年来肿瘤研究的热点,Wnt信号通路包含许多信号成员蛋白,其中任何1个成员蛋白的突变或异常均可激活Wnt信号通路引起细胞异常增殖而导致肿瘤的发生。为此,针对Wnt信号通路不同基因靶点的高特异性基因药物开发以及肿瘤的分子诊断也相继出现。本文回顾近年来相关文献,就Wnt信号通路及其与肿瘤的关系和Wnt信号通路为靶点的肿瘤基因治疗3个方面做一综述。     

Molecular pathogenesis of childhood brain tumors

In the last decade, the molecular biology revolution has advanced considerably. These advances have enhanced our understanding of the genetic underpinnings of human brain tumors in general, and pediatric brain tumors in particular. We now know that many pediatric brain tumors arise from disturbances in developmentally regulated signaling pathways. The medulloblastoma, a tumor in which the developmental Hedgehog and WNT pathways have gone awry, is a prime example of this. New techniques in genetic engineering have allowed for the creation of sophisticated mouse models of brain tumors that recapitulate the human disease. Many laboratories are now using cDNA microarrays to study the expression level of thousands of genes that may be aberrantly expressed in brain tumors when compared to normal control cells. In the next decade, the use of several new molecular techniques to establish brain tumor diagnoses will likely become standard tools in the diagnostics and treatment stratification of children with central nervous system tumors.     

Targeted molecular imaging in oncology: focus on radiation therapy

Anatomically based technologies (computed tomography scans, magnetic resonance imaging, and so on) are in routine use in radiotherapy for planning and assessment purposes. Even with improvements in imaging, however, radiotherapy is still limited in efficacy and toxicity in certain applications. Further advances may be provided by technologies that image the molecular activities of tumors and normal tissues. Possible uses for molecular imaging include better localization of tumor regions and early assay for the radiation response of tumors and normal tissues. Critical to the success of this approach is the identification and validation of molecular probes that are suitable in the radiotherapy context. Recent developments in molecular-imaging probes and integration of functional imaging with radiotherapy are promising. This review focuses on recent advances in molecular imaging strategies and probes that may aid in improving the efficacy of radiotherapy.     

Management of AIDS-related Kaposi's sarcoma

The advent of highly active antiretroviral therapy (HAART) has lead to a substantial reduction in the prevalence, morbidity, and mortality associated with AIDS-related Kaposi's sarcoma. Similarly, concomitant advances in chemotherapy and supportive-care protocols have allowed for Kaposi's sarcoma to be managed more effectively in comparison with the pre-HAART era. Furthermore, developments in our understanding of the pathogenesis of Kaposi's sarcoma have identified several molecular targets that can potentially provide new therapeutic strategies. This Review discusses the role of conventional chemotherapeutic and immunomodulatory agents in the treatment of Kaposi's sarcoma and summarises the current status and future prospects of novel molecularly targeted agents in the treatment of this disease.     

Novel approaches to locally advanced unresectable non-small cell lung cancer.

The management of advanced non-small cell lung cancer (NSCLC) is rapidly evolving. Advances in combined chemo-radiation therapy have led to improvements in patient survival which are statistically significant, but most patients still succumb to their disease. New chemotherapeutic agents, such as taxanes (paclitaxel, docetaxel), topoisomerase inhibitors (topotecan, irinotecan), and novel analogs (gemcitabine, vinorelbine), may offer the promise of improved outcome, but have not yet been tested in phase III trials. Molecular therapeutics, such as gene therapy, drugs that target specific oncogene activation (such as Ki-ras inactivation by farnesyl transferase inhibitors), and hypoxic cell toxins (such as tirapazamine), are in clinical trials. The optimum use of these agents awaits more rapid and widespread molecular diagnostics. Finally, technological advances in radiotherapy will allow higher tumor doses, while minimizing doses to dose-limiting normal structures, such as the esophagus, normal lung and heart. We describe a move towards molecular strategies, both for therapy and diagnostics, that may result in more effective treatment. While the outcome for patients with advanced non-small cell lung carcinoma is still poor, new agents are being developed rapidly and offer the hope of improved survival.     

Novel Directions in Adjuvant Chemotherapy for Early Stage Epithelial Ovarian Cancer

Treatment of early stage ovarian cancer remains controversial despite advances in chemotherapeutic options.Over the past 30 years, molecular and clinicopathologic studies accelerated and treatment of ovarian cancer hasundoubtedly improved although there is a debate as to whether this impacts outcome or not. More recently, theintroduction of targeted therapy started a new era. Probably it is because early stage disease comprises a smallportion of the epithelial ovarian cancer, studies have mostly ignored this group and still there is no clear consensusregarding systemic treatment of early-stage lesions. However this group of patients has the best chance of cure.In this review, we focus on current developments in the treatment of early stage ovarian cancer and query theoptions.