1,721,020 research outputs found
Precision medicine for metastatic breast cancer
Get PDFGenomic studies have shown that large numbers of candidate targets are observed in breast cancer. Nevertheless, only a few of them are validated as relevant targets in clinical studies. Estrogen receptor (ER) and HER2 expressions could be associated with a level I evidence. Beyond ER and HER2, BRCA and PIK3CA mutations (when targeted with alpha-specific PI3K inhibitors) could be considered as promising targets in breast cancer since they have been associated with objective responses in phase I/II trials. In addition to these four molecular alterations, several others have shown promising results in preclinical studies and are being investigated in clinical trials. These genomic alterations include AKT1, ERBB2, and ESR1 mutations. These considerations highlight the lack of evidence for using multiplex technologies to individualize therapy in metastatic breast cancer. Sequencing multiple genes to treat metastatic breast cancer is very promising but should be done in the context of clinical trials, either to enrich phase I/II trials in patients with genomic alterations or to show medical usefulness of new biotechnologies like next-generation sequencing (NGS). Although most current approaches of precision medicine are aiming at targeting drivers, additional applications could be developed in the future. This includes the identification of DNA repair deficiencies, mechanisms of immune suppression, and identification of minority lethal subclones. Finally, one of the very promising applications of genomics for metastatic breast cancer is the identification of pathway activation or defects at the individual level. For example, gene expression and single nucleotide polymorphisms (SNP) signatures are being developed to detect kinase (such as mammalian target of rapamycin [mTOR]/CDK4) activations or DNA repair deficiencies
What to expect from high throughput genomics in metastatic breast cancers?
Get PDFBreast cancer is a heterogeneous disease and its genomic characteristics have been widely studied in the
last years. Although several progresses have been made, metastatic disease is still incurable in the
majority of patients. Recent genomic studies have shown that a large number of candidate targets exist in
breast cancer. Currently only two drivers have been validated (ER and HER2), but several others seem to
be associated with objective response, such as PIK3CA mutations, FGFR1 amplifications, AKT1 mutations,
EGFR amplifications and ERBB2 mutations. Beside driver identification, many other applications can be
developed for genomics such as identification of lethal subclones, DNA repair defects or immune
response against tumor. Most of the precision medicine programs currently use targeted sequencing.
Nevertheless, whole exome sequencing, RNA sequencing, gene expression analysis, phosphoprotein
detection, SNP arrays and ctDNA sequencing have been also proposed in clinical trial
The use of bevacizumab in non-small cell lung cancer: an update
Get PDFLung cancer is the leading cause of cancer-related death worldwide, with approximately 1.2 million deaths annually. The standard-of-care in patients with advanced disease is platinum-based doublet chemotherapy. Recent advances in the understanding of biological mechanisms of tumor growth have allowed for identification of some molecular targets for cancer treatment, such as vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). VEGF is a pro-angiogenetic factor, which binds membrane receptors, and whose intra-cytoplasmatic domain presents tyrosine kinase activity. Pathological angiogenesis promotes tumor growth and metastasis. Targeted action against angiogenesis can lead to regression or normalization of neovascular structures and to inhibition of new blood vessel growth. The most commonly used mechanism is mediated by bevacizumab, a monoclonal antibody that selectively binds to VEGF and prevents interaction with its receptor. Currently bevacizumab is the only anti-angiogenic agent approved for the first-line treatment of non-small cell lung cancer (NSCLC) in selected patients. In the present review, we discuss the most important trials that demonstrate the efficacy and safety of bevacizumab. We also present an overview of the types of patients eligible for this treatment and a cost-effectiveness analysis. In conclusion, the possibility of administering a treatment with bevacizumab must be carefully analyzed case by case. It is important to identify those patients who can really benefit from the use of this drug, through the identification of specific response markers
Hyperprogressive Disease and Early Hypereosinophilia After Anti-PD-1 Treatment: A Case Report.
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Recent advances for the treatment of pancreatic and biliary tract cancer after first-line treatment failure
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Evolving treatments for advanced gastric cancer: appraisal of the survival trend
No full textWe analysed the results of the main clinical studies looking at patients with advanced gastric or esophagogastric junction cancer, in order to differentiate between what is already clinical evidence and what is a promise for the cure of such patients. Thus, achievements from key studies, which had been purposely directed at chemotherapy, molecular target therapies and immunotherapy in both first and second-line setting were analysed. Metronomic chemotherapy, which consists of the administration of continuative low-dose anticancer drugs, was considered also. It was found that patients included in experimental arms of randomized trials compared with controls have often benefited from a statistically significant extension of overall survival. However, further studies are awaited to bring new drugs into clinical practice and to validate candidate biomarkers predictive of response
Gastric Metastases From Testicular Cancer: Case Report and Review of Literature
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Esophageal stenosis: a differential diagnosis between esophageal cancer and metastasis from other neoplasia
Get PDFBACKGROUND:
The occurrence of radiological mediastinal lymphadenopathy as the only evidence of tumor recurrence of cervical carcinoma is very rare. We report on such a case with stenosis of the esophagus.
CASE REPORT:
A 36-year-old Caucasian woman, without any relevant history of gynecological cancer, underwent a trans-vaginal ultrasound with evidence of any cervical lesion locally extended. After histologically-proven diagnosis of squamous cell carcinoma of the cervix uterine, the patient was treated by neoadjuvant chemoradiation, followed by total abdominal hysterectomy with bilateral salpingoophorectomy. A subsequent close follow-up was negative for recurrence of disease until December 2008, two years after diagnosis. At that period, the patient experienced cough and severe dysphagia and for this reason she underwent several examinations including esophagogastroduodenoscopy, whole-body computed tomographic scan and bronchoscopy with transbronchial needle aspiration. Histology led to diagnosis of recurrence of cervical cancer, HPV31-positive, in multiple mediastinal lymphnodes, with infiltration of the esophageal mucosa.
CONCLUSION:
Mediastinal lymphade-nopathy in patients with a history of cervical carcinoma should be suspicious of metastatic disease, even if there is no radiological evidence of distant metastases
A rare case of palatin tonsillar metastasis from small cell lung cancer
Get PDFTonsillar metastases are absolutely rare. Small cell lung cancer (SCLC) is known to be the most frequent histological type of tonsillar metastases, however the way of tumor cells spreading to tonsil remains controversial. We described a case report of 76-year-old man with SCLC and tonsillar metastases, to highlight the importance of oral cavity evaluation as a part of a clinical exam and to show the rare tumor cells spreading
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