Showing papers by "Laura D. Locati published in 2013"
TL;DR: The authors review the current field concerning the RET gene and protein, its involvement in cancer and the preclinical and clinical studies which highlight its role as a potentially important therapeutic target for several cancers.
Abstract: Introduction: The RET gene encodes a receptor tyrosine kinase essential for ontogenesis of the enteric nervous system and kidney. Following identification of RET, it was found that somatic rearrangements of this gene, conventionally designated as RET/PTC, are frequently present in papillary thyroid carcinoma. Subsequently, activating germ line point mutations of RET were identified as being responsible for the hereditary medullary thyroid carcinoma syndromes MEN2A, MEN2B and FMTC. RET rearrangements have recently been identified in a small fraction of lung adenocarcinomas.Area covered: The authors review the current field concerning the RET gene and protein, its involvement in cancer and the preclinical and clinical studies which highlight its role as a potentially important therapeutic target for several cancers.Expert opinion: Many multitargeted inhibitors which crossreact with RET have been developed and investigated in clinical trials targeting many cancer indications. In particular, VEGFR/PDGFR inhib...
42 citations
16 May 2013
TL;DR: Future trials investigating concurrent chemotherapy and radiation, as well as the use of targeted agents based on evolving molecular discoveries, will elucidate optimal personalized approaches for this challenging disease.
Abstract: Malignant salivary gland tumors make up a small proportion of malignancies worldwide, yet vary widely in terms of histology, patterns of spread, and recurrence. A better understanding of this variability will guide appropriate treatment recommendations and lead to improved outcomes. Recent molecular genetic studies have uncovered a translocation-generated gene fusion network in salivary gland carcinomas that can be used for diagnosis, treatment decisions, and development of specific targeted therapies. The gene fusions encode novel fusion oncoproteins that function as transcriptional coactivators, tyrosine kinase receptors, and transcription factors involved in growth-factor signaling and cell-cycle regulation. While surgery currently is the primary therapy for operable tumors, radiation plays an important role in the postoperative setting, as well as in the definitive setting for inoperable lesions. An awareness of the risk factors for tumor recurrence and spread is important for both adjuvant therapy referrals and for radiation treatment planning purposes. Additionally, chemotherapy is being used increasingly in both the concurrent setting as a radiosensitizer, as well as in the palliative setting for metastatic tumors. Future trials investigating concurrent chemotherapy and radiation, as well as the use of targeted agents based on evolving molecular discoveries, will elucidate optimal personalized approaches for this challenging disease.
42 citations
TL;DR: Functional p53 may predict PFL-chemotherapy efficacy, offering a possible increase in survival when induction chemotherapy is given to a selected population.
34 citations
TL;DR: The most relevant causes of failures were suboptimal target definition and target coverage as well as a longer than planned overall treatment time.
Abstract: Aim: To analyze the patterns of locoregional failure following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) at our institution, as part of an internal quality assurance program. We aimed to investigate the potential existence of a correlation between any part of the IMRT process and clinical outcome. Methods & materials: A total of 106 non-metastatic NPC patients consecutively treated with IMRT (with or without chemotherapy) were analyzed. Radiotherapy was administered using a sequential or simultaneous integrated boost approach at the total prescribed dose of 66–70 Gy (2.00–2.12 Gy per fraction). MRI studies of recurrences were recorded with the planning computed tomography studies to identify volume of failure. Recurrence-related characteristics were analyzed with respect to the original treatment. Failures were classified as ‘in-field’, ‘marginal’ or ‘out-field’ if at least 95, 20–95 or less than 20% of the volume of failure, respectively, was within 95% of the total presc...
27 citations
TL;DR: Improvement in the knowledge of pathogenesis and genetics of ATC led to the development of a variety of new molecules that may be used to treat this disease, including proteasome inhibitors, Aurora kinase inhibitors, vascular targeting agents, and gene therapies.
Abstract: PURPOSE OF REVIEW: Anaplastic thyroid cancer (ATC) is a rare and deadly malignancy. There is a need to speed up and support clinical research. This review article focuses on the new molecules that have been developed for the treatment of this aggressive tumor. RECENT FINDINGS: Improvement in the knowledge of pathogenesis and genetics of ATC led to the development of a variety of new molecules that may be used to treat this disease. In summary, these molecules are proteasome inhibitors, Aurora kinase inhibitors, vascular targeting agents, and gene therapies. All these molecules demonstrated a potentially therapeutic activity in metastatic ATC. To date, the largest prospective randomized multicenter, open-label, trial was conducted with combretastatin-A4. SUMMARY: More efficient drugs need to be developed through multinational efforts.
26 citations
TL;DR: It emerges that these agents added to chemotherapy in recurrent/metastatic setting do not represent the best approach because of the major side effects, worsened by the complex characteristics of treated patients, and the lack of gain in terms of efficacy.
Abstract: Introduction: Conventional treatments for head and neck squamous cell cancer (HNSCC) are not completely effective and present several issues in terms of toxicity. Treatments available consist of surgery, chemoradiotherapy and biological agents. Areas covered: Tyrosine-kinase inhibitors (TKIs) alone or in combination, already tested or currently under investigation, will be evaluated together with their time placement along the treatment as well as the disease setting where they were used. Expert opinion: From the results of the main trials on TKIs, it emerges that these agents added to chemotherapy in recurrent/metastatic setting do not represent the best approach because of the major side effects, worsened by the complex characteristics of treated patients, and the lack of gain in terms of efficacy. Targeted agents could better exploit their activity in other settings, such as either before local regional treatment or immediately after to modulate biological effects induced by the treatment itself (surge...
8 citations
TL;DR: A large number of subjects withproven RMSGC not amenable to surgery and/or radiotherapy were enrolled to receive sorafenib and 37 subjects were required to test the null hypothesis that RR will be ≤ 5% versus the alternative that RR ≥ 20% within a two stage Simon design.
Abstract: 6020 Background: Palliative chemotherapy is the standard of care for RMSGCs. However its activity is usually poor especially in adenoid cystic carcinoma (ACC), while in histotypes other than ACC (n...
6 citations
TL;DR: This work aimed to describe molecular markers in DTC that correlate with clinical outcome to axitinib, including best response (BR) (RECIST) and progression free survival (PFS), which were ascertained from corresponding patients.
Abstract: 6066 Background: The VEGFR inhibitor axitinib has demonstrated compelling antitumor activity in advanced RAI-resistant differentiated thyroid cancer (DTC). Biomarkers predicting which patients may ...
1 citations
1 citations
1 citations
TL;DR: The 2 groups were well balanced in regard to recognized prognostic factors (performance status, weight loss, prior radiotherapy, tumor grade, site of primary tumor, residual dis...
Abstract: 6027 Background: First-line chemotherapy with platinum and cetuximab is usually offered to RM-HNSCC pts. In the Extreme trial a median PFS time of 5.6 months was reported. However, a small fraction...