1,721,349 research outputs found
Sequencing Cancer Genome shapes new ways in surgical oncology
No full textProgress in medical and surgical oncology has been slow. Overall survival and cure rates of patients with solid cancer have modestly been improved over the last decade despite the advent of targeted therapy. The advent of next-generation sequencing (NGS) technology allows now whole genome and exome sequencing for the identification of unbiased data about mutations underlying cancer. In addition, new high-throughput techniques provide insights and the role of epigenetic modification, miRNAs deregulation and transcriptome changes that drive tumorigenesis and metastasis. These advances in understanding the structure and function of cancer genome are discussed here along with challenges to reach clinical implications in the multimodal and interdisciplinary treatment of cancer patients
Challenges and expectations for novel biologics discovery in HER2-negative breast cancer
No full textApproximately half a century after the discovery of the human epidermal growth factor (hEGF) and its receptor type 2 (HER2), biologically targeted agents such as trastuzumab and lapatinib may improve oncological outcomes of breast cancer patients whose tumors cancer cells overexpress HER2. The HER2 status has been a standard prognostic factor and patients with breast cancer are classified into HER2-negative and HER2-positive disease. Although prognosis of patients with HER2-positive cancer, as compared to HER2-negative is poorer, the addition of the monoclonal antibody trastuzumab or the tyrosine kinase inhibitor small molecule lapatinib may alter this poor outcome
Early breast cancer: How targeted therapy, genetics and personal genomics may improve local outcomes
No full textBackground: Advances in molecular oncology and genetics start to impact surgical practice in breast cancer. Despite compliance to current guidelines for breast-conserving surgery (BCS) in early breast cancer and multimodal treatment, a subgroup of patients develops ipsilateral breast cancer (IBC) recurrence and/or contralateral breast cancer (CBC). Objective: To identify the high-risk patients for local failure (IBC/ CBC) based on genetics and genomics, to assess the impact of chemoradiotherapy and targeted therapy on IBC/CBC risk and to find out who patients might benefit from aggressive surgery like bilateral mastectomy (BM). Method: All published (1995 - 2009) data on these topics were obtained from PubMed. Results: With emphasis on long-term follow-up results after breast-conserving multimodal treatment, the rate of IBC/CBC as isolated event without any evidence of distant metastasis was substiantial in a specific subgroup. Preclinical and clinical data reveal that at highest risk of IBC/CBC are patients with inherited BRCA1/2 mutations. Particularly these patients with BRCA1/2-causing cancer may benefit from bilateral mastectomy rather than BCS. For the vast majority of patients who are those with familial non-BRCA1/ 2 (BRCA-test negative) or sporadic breast cancer, local failure risk prediction is currently unfeasible. It appears that trastuzumab in HER2-positive patients reduces IBC/CBC rates but longer follow-up data are required for definitive conclusions. Extensive genetic studies including sequencing techniques and more currently genome-wide-association (GWA) studies have already identified novel risk alleles with a series of tumor-initiating single-nucleotide polymorphisms (SNPs). However, although the genetic catalogue with genetic alterations contributing to breast carcinogenesis is nearly to be completed, next challenges include the understanding of genes functional role and the prediction of biologic networks outcomes. Conclusions: Genetic testing in patients with family history guides now decision-making between BCS and BM. In patients with (BRCA mutation testing positive, BM should be considered and discussed with the individual patient. Rapid technological advances provide promises for accurate identification of high-risk patients but multiple challenges should be overcome to predict IBC/CBC risk among familial non-BRCA or sporadic breast cancer and application of bilateral mastectomy
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