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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.

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

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Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer: No significant progress has been made in finding new treatments for decades and platinum-based chemotherapy has for a long time represented the standard of care. This therapeutic scenario has recently changed, thanks to positive results in terms of improvement of overall survival obtained with a combination of checkpoint inhibitors (atezolizumab or durvalumab) with platinum-etoposide in patients with extensive disease. Moreover, nivolumab and pembrolizumab showed antitumor activity and received U.S. FDA approval as single agents in patients pretreated with platinum-based therapy and at least one other therapy. The improvement in the knowledge of the biology of SCLC has led to the development of new experimental therapies that have shown promising results, including poly (ADP-ribose) polymerase (PARP) inhibitors, anti-Notch ligand Delta-like protein 3 (anti-DLL3), antibody–drug conjugates, and aurora kinase inhibitors. Future challenges are the identification of predictive biomarkers for immunotherapy, the definition of the role of new biological agents, and the improvement of integrated approached for limited disease. This Special Issue will highlight the current state of treatment of extensive SCLC, focusing on the biology of SCLC, immune-checkpoint inhibitors, PARP inhibitors, and novel cytotoxic chemotherapy and radiotherapy techniques.

Medicine --- immune checkpoint inhibitors --- extensive-stage small cell lung cancer --- nivolumab --- ipilimumab --- pembrolizumab --- atezolizumab --- durvalumab --- chemotherapy --- small-cell lung cancer --- lobectomy --- pneumonectomy --- radiotherapy --- multimodal treatment --- immunotherapy --- SCLC --- PARP --- DDR --- ICB --- synthetic lethality --- SLFN11 --- STING --- pathology and classification of SCLC --- biology of SCLC --- immune-checkpoint inhibitors in SCLC --- small cell lung cancer --- Immunotherapy --- extensive disease --- lurbinectedin --- gene pathway --- pathobiology --- targeted therapy --- circulating tumor cells --- prognostic biomarker --- targeted agents --- immune checkpoint inhibitors --- extensive-stage small cell lung cancer --- nivolumab --- ipilimumab --- pembrolizumab --- atezolizumab --- durvalumab --- chemotherapy --- small-cell lung cancer --- lobectomy --- pneumonectomy --- radiotherapy --- multimodal treatment --- immunotherapy --- SCLC --- PARP --- DDR --- ICB --- synthetic lethality --- SLFN11 --- STING --- pathology and classification of SCLC --- biology of SCLC --- immune-checkpoint inhibitors in SCLC --- small cell lung cancer --- Immunotherapy --- extensive disease --- lurbinectedin --- gene pathway --- pathobiology --- targeted therapy --- circulating tumor cells --- prognostic biomarker --- targeted agents

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Major technological advances in genomics have made it possible to identify critical genetic alterations in cancer, rendering oncology well along the path to “personalised cancer medicine”. Thanks to developments in genetics, several mutations and gene rearrangements have been identified in patients with endocrine cancers (e.g., thyroid and adrenocortical carcinoma). In particular, each patient can be considered as a unique, individual one, with unique genetic information. The aim of this Special Issue is to offer an overview of exciting new research in the area of endocrine tumours may set the stage for an innovative personalised management and precision medicine modalities for individualised care.New affordable individual genomic analyses, as well as the opportunity to test new compounds in primary cells may allow a personalised management of patients with endocrine malignancies. This approach may improve the prediction of clinical outcome and therapeutic effectiveness, as well as help to avoid the use of ineffective drugs. However, further efforts are needed to obtain an adjustment of clinical management in patients with endocrine cancers that would rely solely or in great part on genetic information. This Special Issue includes basic, translational, and clinical papers on personalised medicine in endocrine malignancies (i.e., thyroid and adrenal), especially focusing on diagnostic and prognostic biomarkers, as well as novel drug targets or targeted treatments, including eventual clinical trials.

Medicine --- papillary thyroid cancer --- SUV PET/CT --- BRAF V600E --- immune checkpoint inhibitors (ICIs) --- ipilimumab --- nivolumab --- prolactinoma --- Cushing’s disease --- aggressive pituitary tumor --- aggressive PitNET --- aggressive pituitary adenoma --- pituitary carcinoma --- adrenocortical cancer --- adrenal adenomas --- adrenal tumors --- p53 --- p27 --- ki-67 --- reticulin --- mitotane --- adjuvant treatment --- recurrence --- recurrence free survival --- timing --- intratumoral heterogeneity --- thyroid tumor --- BRAF --- RET/PTC rearrangements --- RAS mutation --- adrenal cortex --- carcinoma --- angiogenesis --- gene expression --- osteopontin --- hyaluronan synthase 1 --- multikinase inhibitors --- sorafenib --- lenvatinib --- differentiated thyroid cancer --- radioiodine resistance --- predictive marker --- predictors --- response to treatment --- survival --- information needs and preferences --- focus group interview --- personalized medicine --- neuroendocrine tumours --- phaeochromocytoma --- paraganglioma --- molecular clusters --- n/a --- Cushing's disease

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Major technological advances in genomics have made it possible to identify critical genetic alterations in cancer, rendering oncology well along the path to “personalised cancer medicine”. Thanks to developments in genetics, several mutations and gene rearrangements have been identified in patients with endocrine cancers (e.g., thyroid and adrenocortical carcinoma). In particular, each patient can be considered as a unique, individual one, with unique genetic information. The aim of this Special Issue is to offer an overview of exciting new research in the area of endocrine tumours may set the stage for an innovative personalised management and precision medicine modalities for individualised care.New affordable individual genomic analyses, as well as the opportunity to test new compounds in primary cells may allow a personalised management of patients with endocrine malignancies. This approach may improve the prediction of clinical outcome and therapeutic effectiveness, as well as help to avoid the use of ineffective drugs. However, further efforts are needed to obtain an adjustment of clinical management in patients with endocrine cancers that would rely solely or in great part on genetic information. This Special Issue includes basic, translational, and clinical papers on personalised medicine in endocrine malignancies (i.e., thyroid and adrenal), especially focusing on diagnostic and prognostic biomarkers, as well as novel drug targets or targeted treatments, including eventual clinical trials.

Medicine --- papillary thyroid cancer --- SUV PET/CT --- BRAF V600E --- immune checkpoint inhibitors (ICIs) --- ipilimumab --- nivolumab --- prolactinoma --- Cushing's disease --- aggressive pituitary tumor --- aggressive PitNET --- aggressive pituitary adenoma --- pituitary carcinoma --- adrenocortical cancer --- adrenal adenomas --- adrenal tumors --- p53 --- p27 --- ki-67 --- reticulin --- mitotane --- adjuvant treatment --- recurrence --- recurrence free survival --- timing --- intratumoral heterogeneity --- thyroid tumor --- BRAF --- RET/PTC rearrangements --- RAS mutation --- adrenal cortex --- carcinoma --- angiogenesis --- gene expression --- osteopontin --- hyaluronan synthase 1 --- multikinase inhibitors --- sorafenib --- lenvatinib --- differentiated thyroid cancer --- radioiodine resistance --- predictive marker --- predictors --- response to treatment --- survival --- information needs and preferences --- focus group interview --- personalized medicine --- neuroendocrine tumours --- phaeochromocytoma --- paraganglioma --- molecular clusters --- papillary thyroid cancer --- SUV PET/CT --- BRAF V600E --- immune checkpoint inhibitors (ICIs) --- ipilimumab --- nivolumab --- prolactinoma --- Cushing's disease --- aggressive pituitary tumor --- aggressive PitNET --- aggressive pituitary adenoma --- pituitary carcinoma --- adrenocortical cancer --- adrenal adenomas --- adrenal tumors --- p53 --- p27 --- ki-67 --- reticulin --- mitotane --- adjuvant treatment --- recurrence --- recurrence free survival --- timing --- intratumoral heterogeneity --- thyroid tumor --- BRAF --- RET/PTC rearrangements --- RAS mutation --- adrenal cortex --- carcinoma --- angiogenesis --- gene expression --- osteopontin --- hyaluronan synthase 1 --- multikinase inhibitors --- sorafenib --- lenvatinib --- differentiated thyroid cancer --- radioiodine resistance --- predictive marker --- predictors --- response to treatment --- survival --- information needs and preferences --- focus group interview --- personalized medicine --- neuroendocrine tumours --- phaeochromocytoma --- paraganglioma --- molecular clusters

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Biomarkers are of critical medical importance for oncologists, allowing them to predict and detect disease and to determine the best course of action for cancer patient care. Prognostic markers are used to evaluate a patient’s outcome and cancer recurrence probability after initial interventions such as surgery or drug treatments and, hence, to select follow-up and further treatment strategies. On the other hand, predictive markers are increasingly being used to evaluate the probability of benefit from clinical intervention(s), driving personalized medicine. Evolving technologies and the increasing availability of “multiomics” data are leading to the selection of numerous potential biomarkers, based on DNA, RNA, miRNA, protein, and metabolic alterations within cancer cells or tumor microenvironment, that may be combined with clinical and pathological data to greatly improve the prediction of both cancer progression and therapeutic treatment responses. However, in recent years, few biomarkers have progressed from discovery to become validated tools to be used in clinical practice. This Special Issue comprises eight review articles and five original studies on novel potential prognostic and predictive markers for different cancer types.

Medicine --- MSI2 --- OSCC --- oral cancer --- musashi 2 --- prognosis --- N-cadherin --- EMT --- breast cancer --- new metastasis --- eribulin --- blood --- biomarker --- bladder cancer --- immune checkpoint inhibitor --- CD8+ T effector cells --- microRNA --- biomarkers --- head and neck cancer --- laryngeal cancer --- prediction --- metastasis --- lifestyle habit --- chemo-/radio resistance --- therapeutic target --- AKT --- AR --- castration-resistant prostate cancer (CRPC) --- MAPK --- mTOR --- PI3K --- prostate cancer --- therapeutic resistance --- WNT --- miRNA --- melanoma --- melanoma resistance to MAPK/MEK inhibitors --- resistance to immune checkpoint inhibitors --- TNBC --- BRCA1/2 --- HRR --- PDL1 --- TILs --- PI3KCA --- PTEN --- CTCs --- CSC --- pancreatic cancer --- K-RAS oncogene --- oncogene dependency --- targeted therapies --- genomic mutations --- transcriptomics --- metabolomics --- selenoproteins --- cancer --- HUB nodes --- major histocompatibility complex (MHC) --- human leukocyte antigen (HLA) --- antigen processing machinery (APM) molecules --- carcinogenesis --- tumor predisposition --- cancer immunotherapy --- pheochromocytoma --- paraganglioma --- head and neck neoplasms --- head and neck tumors --- genetic syndromes --- mutations --- hyperglycemia --- cardioncology --- nivolumab --- cytokines --- cardiotoxicity --- acetyltransferase --- cancer prognosis --- NAA10 --- n/a