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Second Line Treatment of Non-Small Cell Lung Cancer: Clinical; Pathological and Molecular Aspects of Novel Promising Drugs

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452637 Year: Pages: 84 DOI: 10.3389/978-2-88945-263-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General)
Added to DOAB on : 2018-02-27 16:16:44
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Abstract

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.

The Treatment of Metastatic Non-small Cell Lung Cancer (NSCLC) in New Era of Personalised Medicine

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195435 Year: Pages: 140 DOI: 10.3389/978-2-88919-543-5 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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Lung cancer is the leading cause of cancer related mortality in Canada and USA. Majority of the patients present in advanced stage of the disease and of these only about 2% will be alive at 5 years. NSCLC is the most common form of lung cancer, accounting for approximately 87% of cases. Systemic chemotherapies have been used to treat metastatic NSCLC for decades, but the improvements of outcomes have reached a plateau. Recent advances in understanding signalling pathways for malignant cells, their interconections,the importance of various receptors and biomarkers and the interplay between various oncogenes have led to the development of targeted treatments that are improving both efficacy and safety of the treatments. Knowledge about the advantages of treatments with the targeted agents in metastatic NSCLC is growing rapidly. Combining various targeted agents or sequencing them properly will be important in the era of personalised medicine and overcoming development of the resistence to various targeted agents will be challenging. The importance of a team work,from the diagnosis through various treatments, to supportive care, from the interventional radiologists, pneumologists or surgeons, who have to obtain a satisfactory tumor tissue specimen, to pathologists, radiation and medical oncologists, to supportive care specialists, will be described in our publications. We will cover completely present and future approaches to personalised medicine in this rapidly evolving field of metastatic NSCLC.

Clinical Application of Stereotactic Body Radiotherapy (SBRT): Cranium to Prostate

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889198467 Year: Pages: 85 DOI: 10.3389/978-2-88919-846-7 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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Stereotactic radiosurgery is a relatively recent radiation technique initially developed using a frame-based system in 1949 by a Swedish neurosurgeon, Lars Leksell, for lesions not amendable to surgical resection. Radiosurgery is founded on principles of extreme radiation dose escalation, afforded by precise dose delivery with millimeter accuracy. Building upon the success of frame-based radiosurgery techniques, which were limited to cranial tumors and invasive head-frame placement, advances in radiation delivery and image-guidance have lead to the development of stereotactic body radiotherapy (SBRT). SBRT allows for frameless delivery of dose distributions akin to frame-based cranial stereotactic radiosurgery to both cranial and extra-cranial sites and has emerged as a important treatment strategy for a variety of cancers from the cranium to prostate. Herein we highlight ongoing investigations for the clinical application of SBRT for a variety of primary and recurrence cancers aimed at examining the growing clinical evidence supporting emerging roles for SBRT in the ever growing oncologic armamentarium.

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