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Lung cancer still remains a challenging disease with a higher mortality rate in comparison to other cancers. The discovery of oncogene addicted tumours and targeted therapies responsive to these targets lead to a meaningful change in the prognosis of these diseases. Unfortunately, these newer therapeutic options are reserved to a minor part of lung cancer patients harbouring specific mutations. In the so called wild type population, the first line options bring the median overall survival to go beyond 1 year, and in the population receiving the maintenance therapy over 16 months. Given these results, more than 60% of patients may receive a second line therapy with further opportunities to improve the length and quality of life. For patients not harbouring targetable DNA mutations newer options will be available for second line therapeutic schemes and two major assets seem to be promising: immune modulation and anti-angiogenetic agents. In particular, anti PD1/PDL1 antibodies, VEGFR antibodies and TKIs, these latter combined with standard chemotherapy docetaxel advance the median overall survival of 12 months. These drugs have a different mechanism of action, various adverse events and their activity is different depending on the types of population. However, the biomarkers’ activity and efficacy prediction are not fully or totally understood. In addition, also for patients with DNA targetable mutations new drugs seems to be promising for the use in the second line therapeutic protocols. In particular, drugs selectively directed against ALK translocation and mutational events and EGFR T790M secondary mutations seems to be very promising. In this Research Topic we critically discuss the older therapies and the historical development of second line, putting in to perspective the new agents available in clinical practice. We discuss their importance from a clinical point of view, but also consider and exploit the complex molecular mechanisms responsible of their efficacy or of the subsequently observed resistance phenomena. In this perspective, the undercovering and characterization of novel predictive biomarkers by NGS technology, the characterization of novel actors in the signal transduction pathway modulating the response of the cells, the optimization of new diagnostic tool as the evaluation of liquid biopsy and the implementation of more suitable pre-clinical models are crucial aspects dissected too. Nivolumab, nintedanib and ramucirumab probably will give the opportunity to improve the efficacy outcomes for the treatment of wild type tumours in second line therapeutic schemes, but many aspects should be debated in order that these agents are made available to patients, planning ahead a therapeutic strategy, beginning from the first line therapy, to the subsequent ones in a logical and affordable manner. As well, for treatment of mutated tumours, mutated EGFR irreversible inhibitors such as rociletinib and AZD9291, and ALK targeting drugs ceritinib and alectinib will also play an important role in the immediate future. Probably the right way is to give all the available opportunities to patients, but challenges and pitfalls should be carefully debated, and by launching this Research Topic we tried to give some practical insights in this changing landscape.

Non-Small Cell Lung Cancer --- Second-Line Treatment --- Afatinib --- Nintedanib --- Alectinib --- Dacomitinib --- Nivolumab --- Tyrosine Kinase Inhibitor --- Immunotherapy --- Liquid Biopsy

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The deficits of mammography and the potential of noninvasive diagnostic testing using circulating miRNA profiles are presented in our first review article. Exosomes are important in the transfer of genetic information. The current knowledge on exosome-associated DNAs and on vesicle-associated DNAs and their role in pregnancy-related complications is presented in the next article. The major obstacle is the lack of a standardized technique for the isolation and measurement of exosomes. One review has summarized the latest results on cell-free nucleic acids in inflammatory bowel disease (IBD). Despite the extensive research, the etiology and exact pathogenesis are still unclear, although similarity to the cell-free ribonucleic acids (cfRNAs) observed in other autoimmune diseases seems to be relevant in IBD. Liquid biopsy is a useful tool for the differentiation of leiomyomas and sarcomas in the corpus uteri. One manuscript has collected the most important knowledge of mesenchymal uterine tumors and shows the benefits of noninvasive sampling. Microchimerism has also recently become a hot topic. It is discussed in the context of various forms of transplantation and transplantation-related advanced therapies, the available cell-free nucleic acid (cfNA) markers, and the detection platforms that have been introduced. Ovarian cancer is one of the leading serious malignancies among women, with a high incidence of mortality; the introduction of new noninvasive diagnostic markers could help in its early detection and treatment monitoring. Epigenetic regulation is very important during the development of diseases and drug resistance. Methylation changes are important signs during ovarian cancer development, and it seems that the CDH1 gene is a potential candidate for being a noninvasive biomarker in the diagnosis of ovarian cancer. Preeclampsia is a mysterious disease—despite intensive research, the exact details of its development are unknown. It seems that cell-free nucleic acids could serve as biomarkers for the early detection of this disease. Three research papers deal with the prenatal application of cfDNA. Copy number variants (CNVs) are important subjects for the study of human genome variations, as CNVs can contribute to population diversity and human genetic diseases. These are useful in NIPT as a source of population specific data. The reliability of NIPT depends on the accurate estimation of fetal fraction. Improvement in the success rate of in vitro fertilization (IVF) and embryo transfer (ET) is an important goal. The measurement of embryo-specific small noncoding RNAs in culture media could improve the efficiency of ET.

breast cancer --- screening --- liquid biopsy --- omics --- multi-level diagnostics --- individualized patient profile --- miRNA --- mammography --- predictive and preventive approach --- personalized medicine --- cell-free DNA --- exosomes --- extracellular vesicles --- fetal DNA --- preeclampsia --- growth retardation --- gestational diabetes mellitus --- miRNA --- piRNA --- NGS --- RT-PCR --- embryo culture medium --- C19MC microRNA --- expression --- exosomes --- fetal growth restriction --- gestational hypertension --- plasma --- prediction --- preeclampsia --- pregnancy-related complications --- screening --- non-invasive prenatal testing --- statistical models --- z-score --- cell-free nucleic acids --- circulating nucleic acids --- cell-free DNAs --- cell-free RNAs --- exosomes --- inflammatory bowel disease --- neutrophil extracellular traps --- NETosis --- liquid biopsy --- cell-free nucleic acids --- circulating tumor cells --- leiomyomas --- sarcomas --- leiomyosarcomas --- exosomes --- NIPT --- fetal fraction --- statistical methods --- DNA --- maternal serum screening --- fetal cells --- liquid biopsy --- pyrosequencing --- ovarian cancer --- CDH1 --- PTEN --- PAX1 --- RASSF1 --- cfDNA --- cell-free DNA --- nuclease activity --- aging --- obesity --- gender differences --- copy number variants --- next generation sequencing --- non-invasive prenatal testing --- population study --- microchimerism --- solid organ transplantation --- hematopoietic stem cell transplantation --- genetic marker --- single nucleotide polymorphism --- deletion/insertion polymorphism --- ovarian cancer --- circulating miRNA --- blood plasma --- NanoString --- network analysis --- biomarker --- n/a

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This Special Issue of Cancers (Basel) is mainly dedicated to selecting papers from the talks given during the first Joint Meeting on Lung Cancer (JMLC) between the MD Anderson Cancer Center (Houston, Texas USA) and the Hospital University Federation (HUF) OncoAge (University Côte d’Azur, Nice, France) (Nice, September 2018). The central theme of JMLC is to discuss new advances and exchange ideas regarding lung cancer. Notably, the talks covered different topics on new therapeutic strategies (targeted therapy and immuno-oncology), molecular and cellular biology, biomarkers, and the epidemiology of lung cancer. Special attention was also given to lung cancer in elderly patients. The articles published in this Special Issue covered subjects such as the assessment of new biomarkers and new approaches for the early detection of lung cancer, epidemiological data, and emphasized a place for the newly characterized cellular pathways in lung cancer, which opens room for therapeutic perspectives for lung cancer patients.

cancer --- older adults --- geriatric assessment --- geriatric interventions --- non-small cell lung cancer --- non-smoker --- tumor microenvironment --- targeted treatment --- lung cancer --- artificial intelligence --- screening --- lncRNA --- MALAT1 --- metastasis --- bioinformatics --- integrated approaches --- lung cancer --- rational therapy --- immune profiling --- cancer tissues --- multiplexed methodologies --- image analysis --- spatial analysis --- aging --- cancer --- optimization --- research --- education --- elderly --- well-being --- circulating tumor cells --- liquid biopsy --- lung cancer --- personal medicine --- techniques --- xenograft --- multiplexed --- brightfield --- chromogenic --- fluorescence --- molecular --- immune profiling --- immune-oncology --- digital --- lung cancer --- lung adenocarcinoma --- macrophage --- immunotherapy --- interleukin-1? and immunometabolism --- lung cancer --- EGFR mutations --- EGFR TKIs --- non-coding RNAs --- microRNAs --- long non-coding RNAs --- hormones --- hormone-like action --- non-small cell lung cancer --- immunotherapy --- PD-1/PD-L1 checkpoint blockade --- CD8 T Cells --- immune blockade --- NSCLC --- reversal of EMT --- tumor microenvironment --- tumor plasticity --- TNBC

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Treatment strategies for breast cancer are wide-ranging and often based on a multi-modality approach, depending on the stage and biology of the tumour and the acceptance and tolerance of the patient. They may include surgery, radiotherapy, and systemic therapy (endocrine therapy, chemotherapy, and targeted therapy). Advances in technologies such as oncoplastic surgery, radiation planning and delivery, and genomics, and the development of novel systemic therapy agents alongside their evaluation in ongoing clinical trials continue to strive for improvements in outcomes. In this Special Issue, we publish a collection of studies looking at all forms of therapeutic strategies for early and advanced breast cancer, focusing on their outcomes, notably survival.

advanced breast cancer --- metastatic --- chemotherapy --- antihormone therapy --- HER2 c-erbB2 --- HER2/neu --- trastuzumab --- pertuzumab --- T-DM1 --- lapatinib --- LKB1 --- Breast Cancer --- Older women --- Metformin --- Endocrine therapy --- breast cancer --- breast-conserving therapy --- mastectomy --- outcome --- comparative effectiveness --- metastatic breast cancer --- liquid biopsy --- cell-free DNA --- next-generation sequencing --- circulating tumor cells --- overdiagnosis --- mammography screening --- invasive breast cancer --- zero-inflated Poisson regression model --- breast cancer --- stage IV --- incidence --- tumor biology --- NCDB --- SEER --- Src kinase --- basal-like breast cancer --- cMet --- breast cancer --- radiotherapy --- lymph-node ratio --- disease-free survival --- physical activity --- breast cancer survivors --- physical function --- social well-being --- exercise characteristics --- APOBEC3B --- gene expression --- breast cancer --- ductal carcinoma in situ --- infiltrating breast cancer --- PIK3CA --- ERCC1 --- anthracycline resistance --- taxane sensitivity --- breast cancer --- colorectal cancer --- relative survival --- older patients --- geriatric oncology --- cancer treatment --- metastatic breast cancer --- lactate dehydrogenase --- serum biomarker --- LDH --- monitoring metastatic breast cancer --- palbociclib --- ribociclib --- abemaciclib --- fulvestrant --- aromatase inhibitors --- metastatic breast cancer --- contralateral prophylactic mastectomy --- contralateral breast cancer --- BRCA --- CHEK2 --- PALB2 --- ATM --- mutation carriers --- family history --- survival --- breast cancer --- young women --- histone deacetylase --- HDAC5 inhibitors --- LMK-235 --- breast cancer --- cyclin E --- older patients --- biomarker --- tumor biology --- prognosis --- survival --- n/a