Abstract：
BACKGROUND:Patients with BRAF mutation-positive advanced melanoma respond well to matched therapy with BRAF or MEK inhibitors, but often quickly develop resistance. METHODS:Tumor tissue from ten patients with advanced BRAF mutation-positive melanoma who achieved partial response (PR) or complete response (CR) on BRAF and/or MEK inhibitors was analyzed using next generation sequencing (NGS) assay. Genomic libraries were captured for 3230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to average median depth of 734X with 99% of bases covered >100X. RESULTS:Three of the ten patients (median number of prior therapies = 2) attained prolonged CR (duration = 23.6+ to 28.7+ months); seven patients achieved either a PR or a short-lived CR. One patient who achieved CR ongoing at 28.7+ months and had tissue available close to the time of initiating BRAF inhibitor therapy had only a BRAF mutation. Abnormalities in addition to BRAF mutation found in other patients included: mutations in NRAS, APC and NF1; amplifications in BRAF, aurora kinase A, MYC, MITF and MET; deletions in CDKN2A/B and PAX5; and, alterations in RB1 and ATM. Heterogeneity between patients and molecular evolution within patients was noted. CONCLUSION:NGS identified potentially actionable DNA alterations that could account for resistance in patients with BRAF mutation-positive advanced melanoma who achieved a PR or CR but whose tumors later progressed. A subset of patients with advanced melanoma may harbor only a BRAF mutation and achieve a durable CR on BRAF pathway inhibitors.
journal_name
BMC Cancerjournal_title
BMC cancerauthors
Wheler J,Yelensky R,Falchook G,Kim KB,Hwu P,Tsimberidou AM,Stephens PJ,Hong D,Cronin MT,Kurzrock Rdoi
10.1186/s12885-015-1029-zsubject
Has Abstractpub_date
2015-02-18 00:00:00pages
61issn
1471-2407pii
10.1186/s12885-015-1029-zjournal_volume
15pub_type
杂志文章相关文献
BMC CANCER文献大全abstract：BACKGROUND:MicroRNAs (miRNAs) are well recognized as gene regulators and have been implicated in the regulation of development as well as human diseases. miR-143 is located at a fragile site on chromosome 5 frequently deleted in cancer, and has been reported to be down-regulated in several cancers including colon cance...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-12-232
更新日期：2012-06-12 00:00:00
abstract：BACKGROUND:Recurrence of colorectal cancer (CRC) may arise due to the persistence of drug-resistant and cancer-initiating cells that survive exposure to chemotherapy. Proteins responsible for this recurrence include the chemokine receptor CXCR4, which is known to enable CRC metastasis, as well as the cancer-initiating ...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-015-1702-2
更新日期：2015-11-10 00:00:00
abstract：BACKGROUND:Sarcomas are rare malignant tumors. Accurate initial histological diagnosis is essential for adequate management. We prospectively assessed the medical management of all patients diagnosed with sarcoma in a European region over a one-year period to identify the quantity of first diagnosis compared to central...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-10-150
更新日期：2010-04-19 00:00:00
abstract：BACKGROUND:The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs) has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are ...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-4-74
更新日期：2004-10-09 00:00:00
abstract：BACKGROUND:Mucosal melanomas represent about 1% of all melanoma cases and classically have a worse prognosis than cutaneous melanomas. Due to the rarity of mucosal melanomas, only limited clinical studies with metastatic mucosal melanoma are available. Mucosal melanomas most commonly contain mutations in the gene CKIT,...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-14-516
更新日期：2014-07-16 00:00:00
abstract：BACKGROUND:The phenomenon that malignant cells can acquire stemness under specific stimuli, encompassed under the concept of cancer cell plasticity, has been well-described in epithelial malignancies. To our knowledge, cancer cell plasticity has not yet been described in hematopoietic cancers. To illustrate and study c...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-018-4300-2
更新日期：2018-04-02 00:00:00
abstract：BACKGROUND:Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in p...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-11-355
更新日期：2011-08-17 00:00:00
abstract：BACKGROUND:It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. METHODS:To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, g...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-2-7
更新日期：2002-04-15 00:00:00
abstract：BACKGROUND:Pseudomonas fluorescens lectin (PFL) belongs to a recently discovered anti-HIV lectin family and induces anoikis-like cell death of MKN28 gastric cancer cells by causing α2 integrin internalization through recognition of high mannose glycans; however, the detailed anti-cancer mechanism is not fully elucidate...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-016-2099-2
更新日期：2016-02-06 00:00:00
abstract：BACKGROUND:Cancer is an extremely heterogeneous group of diseases traditionally categorized according to tissue of origin. However, even among patients with the same cancer subtype the cellular alterations at the molecular level are often very different. Several new therapies targeting specific molecular changes found ...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-12-548
更新日期：2012-11-23 00:00:00
abstract：BACKGROUND:Population attributable risks (PARs) are useful tool to estimate the burden of risk factors in cancer incidence. Few studies estimated the PARs of oral cavity cancer to tobacco smoking alone, alcohol drinking alone and their joint consumption but none performed analysis stratified by subsite, gender or age. ...
journal_title：BMC cancer
pub_type： 杂志文章,多中心研究
doi：10.1186/s12885-015-1841-5
更新日期：2015-10-31 00:00:00
abstract：BACKGROUND:Sorafenib is a multiple receptor tyrosine kinase inhibitor known to prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). Predicting this drug's survival benefits is challenging because clinical responses are rarely measurable during treatment. In this study, we hypothesized that...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-017-3889-x
更新日期：2017-12-19 00:00:00
abstract：BACKGROUND:Maintenance of quality of life is the primary goal during treatment of brain metastases (BM). This is a protocol of an ongoing phase III randomised multicentre study. This study aims to determine the exact additional palliative value of stereotactic radiosurgery (SRS) over whole brain radiotherapy (WBRT) in ...
journal_title：BMC cancer
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1186/s12885-017-3494-z
更新日期：2017-07-25 00:00:00
abstract：BACKGROUND:New Zealand and Australia have the highest incidence and mortality rates from cutaneous melanoma in the world. The predominantly fair-skinned New Zealanders and Australians both enjoy sun, tanned skin and the outdoors, and differences in these activities among generations have been important determinants of ...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-13-372
更新日期：2013-08-06 00:00:00
abstract：BACKGROUND:Cancer stem cell (CSC) hypothesis has not been well demonstrated by the lack of the most convincing evidence concerning a single cell capable of giving rise to a tumor. The scarcity in quantity and improper approaches for isolation and purification of CSCs have become the major obstacles for great developmen...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-8-135
更新日期：2008-05-14 00:00:00
abstract：BACKGROUND:Colorectal cancer is the second most common cause of cancer deaths for both men and women, and the third most common cause of cancer in the U.S. Toxicity of current chemotherapeutic agents for colorectal cancer, and emergence of drug resistance underscore the need to develop new, potentially less toxic alter...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-016-2861-5
更新日期：2016-12-08 00:00:00
abstract：BACKGROUND:Activating transcription factor-3 (ATF3) is involved in the complex process of cellular stress response. However, its exact role in cancer is discussed controversially because both tumor suppressive and oncogenic effects have been described. Here we followed-up on our previous observation that inhibition of ...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-10-668
更新日期：2010-12-03 00:00:00
abstract：BACKGROUND:Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic ant...
journal_title：BMC cancer
pub_type： 临床试验,杂志文章
doi：10.1186/s12885-019-5760-8
更新日期：2019-06-11 00:00:00
abstract：BACKGROUND:Estrogen receptor (ER) expression is important for treatment selection and prognostication of breast cancer patients. Although the metastases are the main targets of endocrine therapy, ER status is often based on the primary tumor. However, ER expression in breast cancer primary lesion may not match with its...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-018-5217-5
更新日期：2018-12-27 00:00:00
abstract：BACKGROUND:Surgical resection remains the only curative treatment for pancreatic cancer and is associated with significant post-operative morbidity and mortality. Patients eligible for surgery, increasingly receive neo-adjuvant therapy before surgery or adjuvant therapy afterward, inherently exposing them to toxicity. ...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-020-07733-0
更新日期：2021-01-09 00:00:00
abstract：BACKGROUND:The development and evaluation of new therapeutic approaches for malignant mesothelioma has been sparse due, in part, to lack of suitable tumor models. METHODS:We established primary mesothelioma cultures from pleural and ascitic fluids of five patients with advanced mesothelioma. Electron microscopy and im...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-015-1362-2
更新日期：2015-05-08 00:00:00
abstract：BACKGROUND:It is well known that estrogen receptor α (ERα) participates in the pathogenic progress of breast cancer, hepatocellular carcinoma and head and neck squamous cell carcinoma. In neuroblastoma cells and related cancer clinical specimens, moreover, the ectopic expression of ERα has been identified. However, the...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-015-1495-3
更新日期：2015-06-30 00:00:00
abstract：BACKGROUND:Pancreatic adenocarcinoma is one of the most dreaded cancers with very low survival rate and poor prognosis to the existing frontline chemotherapeutic drugs. Gene therapy in combination with a cytotoxic agent could be a promising approach to circumvent the limitations of previously attempted therapeutic inte...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-14-75
更新日期：2014-02-08 00:00:00
abstract：BACKGROUND:Renal toxicity has been reported with bisphosphonates such as pamidronate and zolidronate but not with ibandronate, in the treatment of breast cancer patients with bone metastasis. One of the patterns of bisphosphonate-induced nephrotoxicity is focal segmental glomerulosclerosis (FSGS) or its morphological v...
journal_title：BMC cancer
pub_type： 杂志文章,评审
doi：10.1186/s12885-015-1536-y
更新日期：2015-07-22 00:00:00
abstract：BACKGROUND:The failure of treatment for breast cancer usually results from distant metastasis in which the epithelial-mesenchymal transition (EMT) plays a critical role. Hyperinsulinemia, the hallmark of Type 2 diabetes mellitus (T2DM), has been regarded as a key risk factor for the progression of breast cancer. Nuclea...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-020-07107-6
更新日期：2020-07-06 00:00:00
abstract：BACKGROUND:RhoC is a small G protein/GTPase and involved in tumor mobility, invasion and metastasis. Previously, up-regulated RhoC expression is found to play an important role in ovarian carcinogenesis and subsequent progression by modulating proliferation, apoptosis, migration and invasion. METHODS:We transfected Rh...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-14-477
更新日期：2014-07-01 00:00:00
abstract：BACKGROUND:E2F1 transcription factor plays a vital role in the regulation of diverse cellular processes including cell proliferation, apoptosis, invasion and metastasis. E2F1 overexpression has been demonstrated in small cell lung cancer (SCLC), and extensive metastasis in early phase is the most important feature of S...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-14-276
更新日期：2014-04-22 00:00:00
abstract：BACKGROUND:Oncotype DX® (ODX) is used to assess risk of disease recurrence in hormone receptor positive, HER2-negative breast cancer and to guide decisions regarding adjuvant chemotherapy. Little is known about how physician factors impact treatment decisions. The purpose of this study was to examine patient and physic...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-020-07355-6
更新日期：2020-09-03 00:00:00
abstract：BACKGROUND:Serine-threonine kinases of the Raf family (A-Raf, B-Raf, C-Raf) are central players in cellular signal transduction, and thus often causally involved in the development of cancer when mutated or over-expressed. Therefore these proteins are potential targets for immunotherapy and a possible basis for vaccine...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/1471-2407-5-15
更新日期：2005-02-09 00:00:00
abstract：BACKGROUND:HER3 mediates drug resistance against epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), resulting in tumor relapse in lung cancers. Previously, we demonstrated that EGFR induces HER3 overexpression, which facilitates the formation of cancer stem-like tumorspheres. However, the cellul...
journal_title：BMC cancer
pub_type： 杂志文章
doi：10.1186/s12885-019-6217-9
更新日期：2019-10-16 00:00:00
