Apmis

doi: 10.1111/apm.12869pmid: N/A

Grauslund, Morten; Scheie, David; Moser, Claus

doi: 10.1111/apm.12952pmid: 30985019

Andreasen, Simon; Kiss, Katalin; Mikkelsen, Lauge Hjorth; Channir, Hani Ibrahim; Plaschke, Christina Caroline; Melchior, Linea Cecilie; Eriksen, Jesper Grau; Wessel, Irene

doi: 10.1111/apm.12901pmid: 30811708

The head and neck region harbor numerous specialized tissues of all lineages giving rise to a plethora of different malignancies. In recent years, new types and subtypes of cancer has been described here due to the recognition of their histological and molecular characteristics. Some have been formally accepted in the most recent classifications from the World Health Organization (WHO) and American Joint Committee on Cancer (AJCC) as distinct diseases due to characteristics in clinical presentation, outcome, and treatment. In particular, this applies to malignancies of the salivary gland, sinonasal tract, and oropharynx. In this overview, we present the most recent developments in the classification, histopathological characteristics, and molecular features of head and neck cancer. The clinical and radiological characteristics, outcome, and treatment options including perspectives for targeted therapies, are discussed.

Scheie, David; Kufaishi, Huda Haidar Abdallah; Broholm, Helle; Lund, Eva Løbner; Stricker, Karin; Melchior, Linea C.; Grauslund, Morten

doi: 10.1111/apm.12916pmid: 30740783

Until recently, diagnostics of brain tumors were almost solely based on morphology and immunohistochemical stainings for relatively unspecific lineage markers. Although certain molecular markers have been known for longer than a decade (combined loss of chromosome 1p and 19q in oligodendrogliomas), molecular biomarkers were not included in the WHO scheme until 2016. Now, the classification of diffuse gliomas rests on an integration of morphology and molecular results. Also, for many other central nervous system tumor entities, specific diagnostic, prognostic and predictive biomarkers have been detected and continue to emerge. Previously, we considered brain tumors with similar histology to represent a single disease entity. We now realize that histologically identical tumors might show alterations in different molecular pathways, and often represent separate diseases with different natural history and response to treatment. Hence, knowledge about specific biomarkers is of great importance for individualized treatment and follow‐up. In this paper we review the biomarkers that we currently use in the diagnostic work‐up of brain tumors.

Umapathy, Ganesh; Mendoza‐Garcia, Patricia; Hallberg, Bengt; Palmer, Ruth H.

doi: 10.1111/apm.12940pmid: 30803032

Over the last decade, anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase (RTK), has been identified as a fusion partner in a diverse variety of translocation events resulting in oncogenic signaling in many different cancer types. In tumors where the full‐length ALK RTK itself is mutated, such as neuroblastoma, the picture regarding the role of ALK as an oncogenic driver is less clear. Neuroblastoma is a complex and heterogeneous tumor that arises from the neural crest derived peripheral nervous system. Although high‐risk neuroblastoma is rare, it often relapses and becomes refractory to treatment. Thus, neuroblastoma accounts for 10–15% of all childhood cancer deaths. Since most cases are in children under the age of 2, understanding the role and regulation of ALK during neural crest development is an important goal in addressing neuroblastoma tumorigenesis. An impressive array of tyrosine kinase inhibitors (TKIs) that act to inhibit ALK have been FDA approved for use in ALK‐driven cancers. ALK TKIs bind differently within the ATP‐binding pocket of the ALK kinase domain and have been associated with different resistance mutations within ALK itself that arise in response to therapeutic use, particularly in ALK‐fusion positive non‐small cell lung cancer (NSCLC). This patient population has highlighted the importance of considering the relevant ALK TKI to be used for a given ALK mutant variant. In this review, we discuss ALK in neuroblastoma, as well as the use of ALK TKIs and other strategies to inhibit tumor growth. Current efforts combining novel approaches and increasing our understanding of the oncogenic role of ALK in neuroblastoma are aimed at improving the efficacy of ALK TKIs as precision medicine options in the clinic.

Rossing, Maria; Sørensen, Claus Storgaard; Ejlertsen, Bent; Nielsen, Finn Cilius

doi: 10.1111/apm.12920pmid: 30689231

Breast cancer was the first to take advantage of targeted therapy using endocrine therapy, and for up to 20% of all breast cancer patients a further significant improvement has been obtained by HER2‐targeted therapy. Greater insight in precision medicine is to some extent driven by technical and computational progress, with the first wave of a true technical advancement being the application of transcriptomic analysis. Molecular subtyping further improved our understanding of breast cancer biology and has through a new tumor classification enabled allocation of personalized treatment regimens. The next wave in technical progression must be next‐generation‐sequencing which is currently providing new and exciting results. Large‐scale sequencing data unravel novel somatic and potential targetable mutations as well as allowing the identification of new candidate genes predisposing for familial breast cancer. So far, around 15% of all breast cancer patients are genetically predisposed with most genes being factors in pathways implicated in genome maintenance. This review focuses on whole‐genome sequencing and the new possibilities that this technique, together with other high‐throughput analytic approaches, provides for a more individualized treatment course of breast cancer patients.

Dimopoulos, Konstantinos; Grønbæk, Kirsten

doi: 10.1111/apm.12906pmid: 30859683

The increasing depth of knowledge about cancer biology throughout the last decades, has underlined the importance of not only genetic aberrations, but also epigenetic abnormalities in cancer cells. The extensive exploration of the cancer epigenome has provided insights into key pathways involved in tumorigenesis, as well as has allowed the development of novel epigenetic therapies. In this review, we will present the important role of epigenetic alterations in hematological diseases, with special focus on epigenetically‐based targeting of hematological malignancies.

Barlebo Ahlborn, Lise; Østrup, Olga

doi: 10.1111/apm.12912pmid: 30784124

Circulating tumor DNA (ctDNA) refers to the fraction of cell‐free DNA in a patient's blood originating from tumor cells. Increased knowledge about tumor genomics, improvements in targeted therapies, and accompanying advances in DNA‐sequencing technologies have increased the interest in using ctDNA as a minimally invasive tool in cancer diagnostics and treatment. Especially, early tumor detection including identification of minimal residual disease and stratification of adjuvant therapy are promising approaches. Also, ctDNA showed to be reliable in treatment monitoring and can be used to assess therapy resistance due to the broad variety of tumor subclones captured in ctDNA. Therefore, using ctDNA in the clinical setting has the potential to improve therapeutic outcomes. In the present review, we summarize the status of ctDNA in oncology with focus of being an alternative to tissue biopsies in early detection and treatment monitoring.

Ehinger, Mats; Pettersson, Louise

doi: 10.1111/apm.12926pmid: 30919505

This review summarizes – with the practicing hematologist in mind – the methods used to determine measurable residual disease (MRD) in everyday practice with some future perspectives, and the current knowledge about the prognostic impact of MRD on outcome in acute myeloid leukemia (AML), excluding acute promyelocytic leukemia. Possible implications for choice of MRD method, timing of MRD monitoring, and guidance of therapy are discussed in general and in some detail for certain types of leukemia with specific molecular markers to monitor, including core binding factor (CBF)‐leukemias and NPM1‐mutated leukemias.

Skov, Marianne; Hansen, Christine Rønne; Pressler, Tacjana

doi: 10.1111/apm.12915pmid: 30761610

Cystic fibrosis (CF) is a severe, monogenic, autosomal recessive disease caused by mutations in the CFTR (cystic fibrosis transmembrane regulator) gene, where disturbed chloride and bicarbonate transportation in epithelial cells results in a multiorgan disease with primarily pulmonary infections and pancreatic insufficiency. In 1968, the Copenhagen CF Center was established, and centralized care of CF patients with monthly control was introduced. Close monitoring and treatment of Pseudomonas lung infection as well as segregation of patients with different infection status improved the clinical outcome as well as survival. Prophylactic basic treatment as well as infection treatments follow specific algorithms. A variety of comorbidities have all along the pulmonary infection control necessitated personalized care, adjusted to the patients′ phenotype. With the introduction of CFTR modulators, the treatment has shifted from prophylactic, symptomatic type toward a new era of precision medicine targeting the basic defect according to the patients′ CFTR genotype. Future directions will focus on further improvement of the CFTR modulators and gene therapy, as well as modifier genes and CF phenotype.