Dramatic Responses Seen with TRK Inhibitor.

Abstract:

:Presenting data on 50 of 55 patients with advanced TRK fusion-positive tumors, researchers reported that 76% of patients responded to the selective pan-TRK inhibitor larotrectinib, and 12% of patients experienced complete responses; 93% of responders remain on therapy. The targeted therapy was well tolerated, with just 13% of patients requiring a dose modification. None of the patients discontinued treatment due to adverse events.

journal_name

Cancer Discov

journal_title

Cancer discovery

authors

doi

10.1158/2159-8290.CD-NB2017-084

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

787

issue

8

eissn

2159-8274

issn

2159-8290

pii

2159-8290.CD-NB2017-084

journal_volume

7

pub_type

杂志文章
  • STATe-of-the-art approach: using oligonucleotide decoys to target the "undruggable".

    abstract::Sen and colleagues have shown for the first time the clinical application of an oligonucleotide decoy targeting the oncogenic transcription factor STAT3 for the treatment of head and neck tumors. Intratumoral injection of decoy effectively reduced the activity of STAT3 as evidenced by a decrease in several of its tran...

    journal_title:Cancer discovery

    pub_type: 评论,杂志文章

    doi:10.1158/2159-8290.CD-12-0310

    authors: Koppikar P,Bromberg J

    更新日期:2012-08-01 00:00:00

  • Evolutionary pathways in BRCA1-associated breast tumors.

    abstract::BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of t...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-11-0325

    authors: Martins FC,De S,Almendro V,Gönen M,Park SY,Blum JL,Herlihy W,Ethington G,Schnitt SJ,Tung N,Garber JE,Fetten K,Michor F,Polyak K

    更新日期:2012-06-01 00:00:00

  • Sending CAR T Cells After Multiple Myeloma.

    abstract::Preliminary results from an ongoing phase I clinical trial in China suggest that chimeric antigen receptor T cells engineered to home in on a protein called BCMA may be a potent therapeutic option for multiple myeloma. The therapy was well tolerated and induced complete, durable responses in patients with relapsed/ref...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-NB2017-088

    authors:

    更新日期:2017-08-01 00:00:00

  • Can the Help Match the Hype? KRASG12C-Specific Inhibitors and Beyond.

    abstract::Hallin and colleagues demonstrate the preclinical activity of the KRASG12C-specific inhibitor MRTX849 in a series of in vitro and in vivo studies with supporting pilot clinical efficacy. Variable responsiveness despite effective KRASG12C inhibition highlights both the promise and potential need for combinatorial strat...

    journal_title:Cancer discovery

    pub_type: 评论,杂志文章

    doi:10.1158/2159-8290.CD-19-1255

    authors: Klempner SJ,Hata AN

    更新日期:2020-01-01 00:00:00

  • Resiliency of lung cancers to EGFR inhibitor treatment unveiled, offering opportunities to divide and conquer EGFR inhibitor resistance.

    abstract::The clinical success of EGF receptor (EGFR) inhibitors in patients with lung cancer is limited by the inevitable development of treatment resistance. Two reports in this issue of Cancer Discovery uncover additional mechanisms by which EGFR-mutant lung cancers escape from EGFR kinase inhibitor treatment. These findings...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-12-0387

    authors: Blakely CM,Bivona TG

    更新日期:2012-10-01 00:00:00

  • New Guideline on Managing Colorectal Cancer.

    abstract::A multidisciplinary panel of experts has issued guidelines that consolidate current evidence on testing for molecular biomarkers in colorectal cancer. The guidelines aim to standardize molecular testing for patients with colorectal cancer and help clinicians identify patients most likely to benefit from targeted treat...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-NB2017-030

    authors:

    更新日期:2017-04-01 00:00:00

  • VHL Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma.

    abstract::Protein-coding mutations in clear cell renal cell carcinoma (ccRCC) have been extensively characterized, frequently involving inactivation of the von Hippel-Lindau (VHL) tumor suppressor. Roles for noncoding cis-regulatory aberrations in ccRCC tumorigenesis, however, remain unclear. Analyzing 10 primary tumor/normal p...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-17-0375

    authors: Yao X,Tan J,Lim KJ,Koh J,Ooi WF,Li Z,Huang D,Xing M,Chan YS,Qu JZ,Tay ST,Wijaya G,Lam YN,Hong JH,Lee-Lim AP,Guan P,Ng MSW,He CZ,Lin JS,Nandi T,Qamra A,Xu C,Myint SS,Davies JOJ,Goh JY,Loh G,Tan BC,Roz

    更新日期:2017-11-01 00:00:00

  • The TP53 Apoptotic Network Is a Primary Mediator of Resistance to BCL2 Inhibition in AML Cells.

    abstract::To study mechanisms underlying resistance to the BCL2 inhibitor venetoclax in acute myeloid leukemia (AML), we used a genome-wide CRISPR/Cas9 screen to identify gene knockouts resulting in drug resistance. We validated TP53, BAX, and PMAIP1 as genes whose inactivation results in venetoclax resistance in AML cell lines...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-19-0125

    authors: Nechiporuk T,Kurtz SE,Nikolova O,Liu T,Jones CL,D'Alessandro A,Culp-Hill R,d'Almeida A,Joshi SK,Rosenberg M,Tognon CE,Danilov AV,Druker BJ,Chang BH,McWeeney SK,Tyner JW

    更新日期:2019-07-01 00:00:00

  • LKB1 Inactivation Promotes ROS-Induced Plasticity in NSCLC.

    abstract::LKB1 inactivation generates a redox imbalance that promotes ADC-to-SCC transdifferentiation in NSCLC. ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-RW2015-089

    authors:

    更新日期:2015-07-01 00:00:00

  • Immune Escape in Breast Cancer During In Situ to Invasive Carcinoma Transition.

    abstract::To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutro...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-17-0222

    authors: Gil Del Alcazar CR,Huh SJ,Ekram MB,Trinh A,Liu LL,Beca F,Zi X,Kwak M,Bergholtz H,Su Y,Ding L,Russnes HG,Richardson AL,Babski K,Min Hui Kim E,McDonnell CH 3rd,Wagner J,Rowberry R,Freeman GJ,Dillon D,Sorlie T,Cous

    更新日期:2017-10-01 00:00:00

  • Metastasis Has Multiple Origins and Occurs Early in Tumorigenesis.

    abstract::Whether metastases were seeded mono- or polyclonally depended on cancer site and treatment. ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-RW2020-082

    authors:

    更新日期:2020-07-01 00:00:00

  • RBM4-regulated alternative splicing suppresses tumorigenesis.

    abstract::RBM4 inhibits cancer cell growth and migration by regulating cancer-associated gene splicing. ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-RW2014-198

    authors:

    更新日期:2014-11-01 00:00:00

  • Tucatinib Impresses in Breast Cancer.

    abstract::Recent results suggest that tucatinib, when combined with trastuzumab and capecitabine, is effective in patients with locally advanced inoperable or metastatic HER2-positive breast cancer who have received prior therapies: In a phase II trial, the drug extended overall survival and progression-free survival compared w...

    journal_title:Cancer discovery

    pub_type: 新闻

    doi:10.1158/2159-8290.CD-NB2019-135

    authors:

    更新日期:2020-01-01 00:00:00

  • Nod for Atezolizumab in Advanced Bladder Cancer.

    abstract::The FDA approved atezolizumab to treat advanced bladder cancer when cisplatin chemotherapy is contraindicated. The approval offers a potentially more effective alternative to carboplatin-based chemotherapy for frail, elderly patients. ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-NB2017-064

    authors:

    更新日期:2017-06-01 00:00:00

  • CD30-Targeted CAR T Cells Show Promise in Pretreated Hodgkin Lymphoma.

    abstract::CD30-directed CAR T cells were safe and produced a 62% overall response rate in Hodgkin lymphoma. ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-RW2020-111

    authors:

    更新日期:2020-09-01 00:00:00

  • Novel molecule targets cytokinesis.

    abstract::Researchers have identified a new compound, OTS964, that blocks cytokinesis. Injections of the compound eliminated human lung tumors that had been transplanted into mice. Clinical trials of OTS964 may start next year. ...

    journal_title:Cancer discovery

    pub_type: 新闻

    doi:10.1158/2159-8290.CD-NB2014-170

    authors:

    更新日期:2015-01-01 00:00:00

  • Insights into Epigenetic Remodeling in VHL-Deficient Clear Cell Renal Cell Carcinoma.

    abstract:: Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the von Hippel-Lindau tumor suppressor gene (VHL), and the functional tumorigenic consequences of this loss have been used to develop therapies for advanced ccRCC, such as targeting activation of the HIF pathway. Yao and colleagues elucidate how ...

    journal_title:Cancer discovery

    pub_type: 评论,杂志文章

    doi:10.1158/2159-8290.CD-17-0971

    authors: Ricketts CJ,Linehan WM

    更新日期:2017-11-01 00:00:00

  • EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing.

    abstract:UNLABELLED:Glioblastomas (GBM) with EGFR amplification represent approximately 50% of newly diagnosed cases, and recent studies have revealed frequent coexistence of multiple EGFR aberrations within the same tumor, which has implications for mutation cooperation and treatment resistance. However, bulk tumor sequencing ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-13-0879

    authors: Francis JM,Zhang CZ,Maire CL,Jung J,Manzo VE,Adalsteinsson VA,Homer H,Haidar S,Blumenstiel B,Pedamallu CS,Ligon AH,Love JC,Meyerson M,Ligon KL

    更新日期:2014-08-01 00:00:00

  • Pembrolizumab Approved for Hodgkin Lymphoma.

    abstract::The FDA has approved pembrolizumab for adults and children with classical Hodgkin lymphoma whose disease is refractory to or has relapsed after at least three prior therapies. The approval marks the first time that a PD-1 inhibitor has been indicated for blood cancers-and for children. ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-NB2017-044

    authors:

    更新日期:2017-05-01 00:00:00

  • Stabilization of a closed kinase conformation induces RAF dimerization.

    abstract::BRAF inhibitors stabilize a closed, rigid RAF kinase conformation that facilitates dimerization. ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-RW2013-114

    authors:

    更新日期:2013-07-01 00:00:00

  • Targeting the Noncoding Genome: Superenhancers Meet Their Kryptonite.

    abstract:: In this study, McKeown and colleagues carried out a genome-wide characterization and stratification of the enhancer landscape in acute myeloid leukemia (AML). The authors' analysis led to the discovery of a novel RARA superenhancer found in a subset of patients with AML, rendering these leukemia cells highly sens...

    journal_title:Cancer discovery

    pub_type: 评论,杂志文章

    doi:10.1158/2159-8290.CD-17-0860

    authors: Wang E,Aifantis I

    更新日期:2017-10-01 00:00:00

  • Recurrent Fusions in MYB and MYBL1 Define a Common, Transcription Factor-Driven Oncogenic Pathway in Salivary Gland Adenoid Cystic Carcinoma.

    abstract:UNLABELLED:Adenoid cystic carcinoma (ACC), the second most common malignancy of salivary glands, is a rare tumor with a bleak prognosis for which therapeutic targets are unavailable. We used RNA sequencing (RNA-seq) to analyze low-quality RNA from archival, formaldehyde-fixed, paraffin-embedded samples. In addition to ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-15-0859

    authors: Brayer KJ,Frerich CA,Kang H,Ness SA

    更新日期:2016-02-01 00:00:00

  • Targeting DNA Damage Response Promotes Antitumor Immunity through STING-Mediated T-cell Activation in Small Cell Lung Cancer.

    abstract::Despite recent advances in the use of immunotherapy, only a minority of patients with small cell lung cancer (SCLC) respond to immune checkpoint blockade (ICB). Here, we show that targeting the DNA damage response (DDR) proteins PARP and checkpoint kinase 1 (CHK1) significantly increased protein and surface expression...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-18-1020

    authors: Sen T,Rodriguez BL,Chen L,Corte CMD,Morikawa N,Fujimoto J,Cristea S,Nguyen T,Diao L,Li L,Fan Y,Yang Y,Wang J,Glisson BS,Wistuba II,Sage J,Heymach JV,Gibbons DL,Byers LA

    更新日期:2019-05-01 00:00:00

  • Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors.

    abstract::HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant so...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-19-1014

    authors: Tsurutani J,Iwata H,Krop I,Jänne PA,Doi T,Takahashi S,Park H,Redfern C,Tamura K,Wise-Draper TM,Saito K,Sugihara M,Singh J,Jikoh T,Gallant G,Li BT

    更新日期:2020-05-01 00:00:00

  • AMG 510 First to Inhibit "Undruggable" KRAS.

    abstract::Amgen's novel small-molecule inhibitor AMG 510 has become the first drug to successfully target a KRAS mutation in patients, according to findings presented at the 2019 American Society of Clinical Oncology Annual Meeting. In a phase I trial, AMG 510 elicited partial responses in half of evaluable patients with KRASG1...

    journal_title:Cancer discovery

    pub_type: 新闻

    doi:10.1158/2159-8290.CD-NB2019-073

    authors:

    更新日期:2019-08-01 00:00:00

  • A combined epigenetic therapy equals the efficacy of conventional chemotherapy in refractory advanced non-small cell lung cancer.

    abstract::A new study by Juergens and colleagues provides the first successful example of a combined epigenetic therapy capable of achieving results similar to those of conventional chemotherapy in refractory metastatic non-small cell lung cancer. Furthermore, the authors describe interesting blood-based DNA methylation biomark...

    journal_title:Cancer discovery

    pub_type: 评论,杂志文章

    doi:10.1158/2159-8290.CD-11-0271

    authors: Rodríguez-Paredes M,Esteller M

    更新日期:2011-12-01 00:00:00

  • Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets.

    abstract:UNLABELLED:Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer that most commonly evolves from preexisting prostate adenocarcinoma (PCA). Using Next Generation RNA-sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, and 5 benign prostate tissue (BEN), and validated findings ...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-11-0130

    authors: Beltran H,Rickman DS,Park K,Chae SS,Sboner A,MacDonald TY,Wang Y,Sheikh KL,Terry S,Tagawa ST,Dhir R,Nelson JB,de la Taille A,Allory Y,Gerstein MB,Perner S,Pienta KJ,Chinnaiyan AM,Wang Y,Collins CC,Gleave ME,Demi

    更新日期:2011-11-01 00:00:00

  • A critical role for fas-mediated off-target tumor killing in T cell immunotherapy.

    abstract::T cell-based therapies have induced cancer remissions, though most tumors ultimately progress, reflecting inherent or acquired resistance including antigen escape. Better understanding of how T cells eliminate tumors will help decipher resistance mechanisms. We used a CRISPR/Cas9 screen and identified a necessary role...

    journal_title:Cancer discovery

    pub_type: 杂志文章

    doi:10.1158/2159-8290.CD-20-0756

    authors: Upadhyay R,Boiarsky JA,Pantsulaia G,Svensson-Arvelund J,Lin MJ,Wroblewska A,Bhalla S,Scholler N,Bot A,Rossi JM,Sadek N,Parekh S,Laganà A,Baccarini A,Merad M,Brown BD,Brody JD

    更新日期:2020-12-17 00:00:00

  • EZH2 Inhibitors: Take It EZy, It Is All About Context.

    abstract::Even in diffuse large B-cell lymphoma (DLBCL), a cancer of professional antigen-presenting cells, response rates to immune checkpoint blockade therapy have been limited. One reason for DLBCL immune evasion is epigenetic repression instead of activation of the antigen-presenting MHC-a dissection of mechanisms underlyin...

    journal_title:Cancer discovery

    pub_type: 评论,杂志文章

    doi:10.1158/2159-8290.CD-19-0090

    authors: Velcheti V,Wong KK,Saunthararajah Y

    更新日期:2019-04-01 00:00:00

  • Drugs, diagnostic tests approved quickly.

    abstract::Accelerated review and greater understanding of tumor biology speed targeted treatments to patients. ...

    journal_title:Cancer discovery

    pub_type: 新闻

    doi:10.1158/2159-8290.CD-ND11-09

    authors: Rose S

    更新日期:2011-10-01 00:00:00