Molecular targeted therapies in breast cancer: Where are we now?

Targeted therapies, in cancer treatment, represent a new generation of drugs that interfere with specific molecular targets (typically proteins) having critical roles to play in tumour growth or progression. The principle of targeted therapy is certainly not new: tamoxifen, a hormonal agent targeted at the estrogen receptor, has been in use for more than 30 years. However, this principle has re-gained significant emphasis with the recent development of new biological agents, such as trastuzumab, which was first approved for the treatment of advanced breast cancer (BC) in 1998. Presently, there are at least three different targeted therapies with well documented activity in advanced BC and all three are now being studied in the adjuvant setting; trastuzumab and bevacizumab are monoclonal antibodies, and lapatinib is a dual inhibitor of HER-1 and HER-2. This paper will review the increasing role of molecular targeted therapies in BC, with a particular focus on those drugs currently being tested in early BC, as well as, on future perspectives.     

miRNA – Therapeutic tool in breast cancer? Where are we now?

Objective

The aim of this study was to review the current knowledge about involvement of microRNAs in breast cancer, and their potential in the clinic, published in scientific journals searched in Pubmed/Medline database until March 2014.

Results

MicroRNAs (miRNAs) are a family of 21–25 nucleotide small RNAs molecules. Currently, it is well known that miRNA plays a key role in all cellular processes of the organism including tumour initiation and progression. Many studies have shown that circulating miRNAs are attractive, easily detectable tumour biomarkers. Breast cancer is one of the most common cancers in the world. It is clinically established that different subtypes may respond differently to therapies, give metastases and present drug resistance. MicroRNAs have a potential as diagnostic, prognostic and therapeutic tools in breast cancer.

Conclusion

Molecular knowledge is crucial for choosing the most effective therapy for individual patients. MicroRNAs holds a great potential in anticancer therapy.     

Comparative Modelling Techniques: Where are we?

The enormous increase in data availability brought about by genomic projects is paralleled by an equally unprecedented increase in the expectations for new medical, pharmacological, environmental and biotechnological discoveries. Whether or not we will be able to meet (at least partially) these expectations will depend on how well we will be able to interpret the data and translate the mono-dimensional information encrypted in genomes into a detailed understanding of its biological meaning at the phenotypic level. The process is far from being trivial, and the obstacles along the road are formidable: even the problem of identifying coding regions in eukaryotic genomes is not completely solved. Far more complex is identification of the function of the encoded proteins, and this will probably represent the most challenging problem for the next generations of scientists.     

Genetic research in osteoporosis: Where are we? Where should we go next?

Fractures resulting from low bone mass and excessive skeletal fragility (osteoporosis) are common worldwide both in males and females, particularly in later years of life. Both fractures, and the most important predictor of fractures, bone mass, are now known to be strongly heritable. This fact, plus the current growth in genetic science, has led to a surge of genetic research in osteoporosis, mostly in the search for genes and their polymorphisms that are responsible for variation in bone mass. Finding the genetic basis underlying variation in bone mass will lead us to deeper understanding of the biology of bone mass accumulation, maintenance and adaptation to load. This, plus finding the genetic basis for overall variation in fracture risk per se, will facilitate the development of interventions, both pharmaceutical and non-pharmaceutical, to prevent and/or treat osteoporosis successfully. This research has produced a rather large number of gene loci that seem to influence bone mass. The challenge now is to refine the statistical genetics and the phenotypes involved so that we can confidently identify those gene loci that truly influence bone mass, and to find ways to study the genetic basis for the most direct disease outcome of interest, fracture.     

Laser hair removal: where are we now?

The hair removal market is evolving rapidly. The goal has always been long-term epilation. Success is dependent on understanding hair biology and physiology and on knowledge of laser physics, skin optics, and tissue preservation with respect to these emerging laser technologies. These topics will be reviewed, as will specific categories of laser systems in the hair removal arena and the clinical aspects of laser hair removal today.     

Detection of the vulnerable coronary atheromatous plaque. Where are we now?

Atherosclerosis is a progressive process with potentially devastating consequences and has been identified as the leading cause of morbidity and mortality, especially in the industrial countries. The underlying mechanisms include endothelial dysfunction, lipid accumulation and enhanced inflammatory involvement resulting in plaque disruption or plaque erosion and subsequent thrombosis. However, it has been made evident, that the majority of rupture prone plaques that produce acute coronary syndromes are not severely stenotic. Conversely, lipid-rich plaques with thin fibrous cap, heavily infiltrated by inflammatory cells have been shown to predispose to rupture and thrombosis, independently of the degree of stenosis. Therefore, given the importance of plaque composition, a continuously growing interest in the development and improvement of diagnostic modalities will promptly and most importantly, accurately detect and characterize the high-risk atheromatous plaque. Use of these techniques may help risk stratification and allow the selection of the most appropriate therapeutic approach.     

Insurance and genetic testing: where are we now?

Basic research will spur development of genetic tests that are capable of presymptomatic prediction of disease, disability, and premature death in presently asymptomatic individuals. Concerns have been expressed about potential harms related to the use of genetic test results, especially loss of confidentiality, eugenics, and discrimination. Existing laws and administrative policies may not be sufficient to assure that genetic information is used fairly. To provide factual information and conceptual principles upon which sound social policy can be based, the Human Genome Initiative established an Ethical, Legal, and Social Issues Program. Among the first areas to be identified as a priority for study was insurance. This paper provides a review of life, health, and disability insurance systems, including basic principles, risk classification, and market and regulatory issues, and examines the potential impact of genetic information on the insurance industry.     

Oxidative stress and neurodegeneration: where are we now?

The brain and nervous system are prone to oxidative stress, and are inadequately equipped with antioxidant defense systems to prevent 'ongoing' oxidative damage, let alone the extra oxidative damage imposed by the neurodegenerative diseases. Indeed, increased oxidative damage, mitochondrial dysfunction, accumulation of oxidized aggregated proteins, inflammation, and defects in protein clearance constitute complex intertwined pathologies that conspire to kill neurons. After a long lag period, therapeutic and other interventions based on a knowledge of redox biology are on the horizon for at least some of the neurodegenerative diseases.     

The wing base of the palaeodictyopteran genus Dunbaria Tillyard: Where are we now?

The structure of insect wing articulation is considered as reliable source of high level characters for phylogenetic analyses. However, the correct identification of homologous structures among the main groups of Pterygota is a hotly debated issue. Therefore, the reconstruction of the wing bases in Paleozoic extinct relatives is of great interest, but at the same time it should be treated with extreme caution due to distortions caused by taphonomic effects. The present study is focused on the wing base in Dunbaria (Spilapteridae). The articulation in Dunbaria quinquefasciata is mainly formed by a prominent upright axillary plate while the humeral plate is markedly reduced. Due to unique preservation of surface relief of the axillary plate, its composition shows a detailed pattern of three fused axillary sclerites and presumable position of the sclerite 3Ax. The obtained structures were compared among Spilapteridae and to other palaeodictyopterans Ostrava nigra (Homoiopteridae) and Namuroningxia elegans (Namuroningxiidae). The comparative study uncovered two patterns of 3Ax in Dunbaria and Namuroningxia, which correspond to their different suprafamilial classification. In contrast to previous studies these new results reveal the homologous structural elements in the wing base between Paleozoic Palaeodictyoptera and their extant relatives of Ephemeroptera, Odonata and Neoptera.     

Predicting loss of evolutionary history: Where are we?

The Earth's evolutionary history is threatened by species loss in the current sixth mass extinction event in Earth's history. Such extinction events not only eliminate species but also their unique evolutionary histories. Here we review the expected loss of Earth's evolutionary history quantified by phylogenetic diversity (PD) and evolutionary distinctiveness (ED) at risk. Due to the general paucity of data, global evolutionary history losses have been predicted for only a few groups, such as mammals, birds, amphibians, plants, corals and fishes. Among these groups, there is now empirical support that extinction threats are clustered on the phylogeny; however this is not always a sufficient condition to cause higher loss of phylogenetic diversity in comparison to a scenario of random extinctions. Extinctions of the most evolutionarily distinct species and the shape of phylogenetic trees are additional factors that can elevate losses of evolutionary history. Consequently, impacts of species extinctions differ among groups and regions, and even if global losses are low within large groups, losses can be high among subgroups or within some regions. Further, we show that PD and ED are poorly protected by current conservation practices. While evolutionary history can be indirectly protected by current conservation schemes, optimizing its preservation requires integrating phylogenetic indices with those that capture rarity and extinction risk. Measures based on PD and ED could bring solutions to conservation issues, however they are still rarely used in practice, probably because the reasons to protect evolutionary history are not clear for practitioners or due to a lack of data. However, important advances have been made in the availability of phylogenetic trees and methods for their construction, as well as assessments of extinction risk. Some challenges remain, and looking forward, research should prioritize the assessment of expected PD and ED loss for more taxonomic groups and test the assumption that preserving ED and PD also protects rare species and ecosystem services. Such research will be useful to inform and guide the conservation of Earth's biodiversity and the services it provides.     

Pim kinases in hematological malignancies: where are we now and where are we going?

The proviral insertion in murine (PIM) lymphoma proteins are a serine/threonine kinase family composed of three isoformes: Pim-1, Pim-2 and Pim-3. They play a critical role in the control of cell proliferation, survival, homing and migration. Recently, overexpression of Pim kinases has been reported in human tumors, mainly in hematologic malignancies. In vitro and in vivo studies have confirmed their oncogenic potential. Indeed, PIM kinases have shown to be involved in tumorgenesis, to enhance tumor growth and to induce chemo-resistance, which is why they have become an attractive therapeutic target for cancer therapy. Novel molecules inhibiting Pim kinases have been evaluated in preclinical studies, demonstrating to be effective and with a favorable toxicity profile. Given the promising results, some of these compounds are currently under investigation in clinical trials. Herein, we provide an overview of the biological activity of PIM-kinases, their role in hematologic malignancies and future therapeutic opportunities.     

50 Years of Women in Cell Biology: Where have we been? Where are we going?

It’s been 50 years since Women in Cell Biology (WICB) was founded by junior women cell biologists who found themselves neither represented at the American Society for Cell Biology (ASCB) presentations nor receiving the information, mentoring, and sponsorship they needed to advance their careers. Since then, gender parity at ASCB has made significant strides: WICB has become a standing ASCB committee, women are regularly elected president of the ASCB, and half the symposia speakers are women. Many of WICB’s pioneering initiatives for professional development, including career panels, workshops, awards for accomplishments in science and mentoring, and career mentoring roundtables, have been incorporated and adapted into broader “professional development” that benefits all members of ASCB. The time has passed when we can assume that all women benefit equally from progress. By strategically, thoughtfully, and honestly recognizing the challenges to women of the past and today, we may anticipate those new challenges that will arise in the next 50 years. WICB, in collaboration with the ASCB, can lead in data collection and access and can promote diversity, equity, and inclusion. This work will be a fitting homage to the women who, half a century ago, posted bathroom stall invitations to the first Women in Cell Biology meetup.