mTOR inhibition, the second generation: ATP-competitive mTOR inhibitor initiates unexpected receptor tyrosine kinase-driven feedback loop.

abstract：:Loss-of-function mutations in JAK1/2 can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned that they may also be involved in primary resistance to anti-PD-1 therapy. JAK1/2-inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 pati...

journal_title：Cancer discovery

authors： Shin DS,Zaretsky JM,Escuin-Ordinas H,Garcia-Diaz A,Hu-Lieskovan S,Kalbasi A,Grasso CS,Hugo W,Sandoval S,Torrejon DY,Palaskas N,Rodriguez GA,Parisi G,Azhdam A,Chmielowski B,Cherry G,Seja E,Berent-Maoz B,Shintaku IP,L

更新日期：2017-02-01 00:00:00

abstract：:The pks+E. coli metabolite colibactin caused a unique mutational signature in intestinal organoids. ...

journal_title：Cancer discovery

authors：

更新日期：2020-05-01 00:00:00

abstract：:Findings from a phase I/IIa study indicate that combining the investigational indoleamine 2,3-dioxygenase 1 inhibitor BMS-986205 with nivolumab is safe and boosts response rates among patients with bladder and cervical cancers. ...

journal_title：Cancer discovery

authors：

更新日期：2018-01-01 00:00:00

abstract：:The FDA granted accelerated approval to palbociclib for the treatment of estrogen receptor-positive, HER2-negative metastatic breast cancer in postmenopausal women who have not yet received endocrine-based therapy. Palbociclib is the first cell cycle-targeting CDK 4/6 inhibitor to reach the market. ...

journal_title：Cancer discovery

authors：

更新日期：2015-04-01 00:00:00

abstract：:According to the final analysis of CLEOPATRA, first-line treatment with pertuzumab plus trastuzumab and docetaxel significantly improves overall survival for patients with HER2-positive metastatic breast cancer. As such, dual HER2 blockade plus chemotherapy should be the standard of care in this setting, researchers s...

journal_title：Cancer discovery

authors：

更新日期：2014-12-01 00:00:00

abstract：:Ceritinib and other second-generation inhibitors have demonstrated promising anticancer activity in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Specifically, they can overcome resistance due to certain gatekeeper mutations acquired following crizotinib exposure. These agents now provi...

journal_title：Cancer discovery

authors： Ramalingam SS,Khuri FR

更新日期：2014-06-01 00:00:00

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

authors： Rodríguez-Paredes M,Esteller M

更新日期：2011-12-01 00:00:00

abstract：:In the plasmaMATCH trial, researchers performed circulating tumor DNA testing on patients with advanced breast cancer and matched those with ESR1, HER2, or AKT1 alterations to targeted therapies. Patients with HER2 and AKT1 mutations experienced response rates greater than 22% with durable benefit. ...

journal_title：Cancer discovery

authors：

更新日期：2020-05-01 00:00:00

abstract：:In this issue of Cancer Discovery, Poulin and colleagues apply structural, biochemical, and biological profiling of two mutants of KRAS, one found most frequently in all cancers (G12D) and one found nearly exclusively in colorectal cancer (A146T). They provide compelling evidence that specific mutations will impart di...

journal_title：Cancer discovery

authors： Hobbs GA,Der CJ

更新日期：2019-06-01 00:00:00

abstract：:A report from the American Cancer Society reveals that colorectal cancer in people younger than 50 continues to increase, a trend that has spread to the 50-to-64 age group for the first time. Multiple lines of evidence indicate that obesity, often pinpointed as the cause, is not the only contributor. ...

journal_title：Cancer discovery

authors：

更新日期：2020-06-01 00:00:00

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

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

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 jus...

journal_title：Cancer discovery

authors：

更新日期：2017-08-01 00:00:00

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

authors：

更新日期：2017-08-01 00:00:00

abstract：:DNA repair deficiencies are common among cancer cells and represent a potential vulnerability that might be exploited by targeting compensatory repair pathways. However, the identification of synthetically lethal combinations of DNA repair defects, although of significant clinical relevance, has been somewhat anecdota...

journal_title：Cancer discovery

authors： Hemann MT

更新日期：2014-05-01 00:00:00

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

authors：

更新日期：2015-01-01 00:00:00

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

authors： Koppikar P,Bromberg J

更新日期：2012-08-01 00:00:00

abstract：:An expert panel recommended approval of Novartis's experimental chimeric antigen T-cell therapy, tisagenlecleucel, for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia. The therapy would be the first of its kind approved for cancer and has the potential to transform standard of...

journal_title：Cancer discovery

authors：

更新日期：2017-09-01 00:00:00

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

authors：

更新日期：2019-08-01 00:00:00

abstract：:The structure of CD20 with the antibody drug rituximab showed the binding mode and 2:2 stoichiometry. ...

journal_title：Cancer discovery

authors：

更新日期：2020-04-01 00:00:00

abstract：:Nuclear hormone receptor targeting suppresses melanoma progression in diverse preclinical models. ...

journal_title：Cancer discovery

authors：

更新日期：2014-05-01 00:00:00

abstract：:According to findings of a study in the Journal of the National Cancer Institute, people with a single-nucleotide polymorphism on chromosome 8q24 who regularly use aspirin can cut their risk of colorectal cancer by about half. ...

journal_title：Cancer discovery

authors：

更新日期：2014-03-01 00:00:00

abstract：:Adding stereotactic ablative radiotherapy (SABR) to standard treatment slowed 6-month disease progression in men with hormone-sensitive metastatic prostate cancer, allowing them to delay androgen deprivation therapy, according to findings from the phase II ORIOLE trial. Larger studies are needed to determine if SABR, ...

journal_title：Cancer discovery

authors：

更新日期：2020-06-01 00:00:00

abstract：:Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently in human cancers, but targeting AKT has been difficult due to the mechanism-based toxicities of inhibitors that target the inactive conformation of AKT. Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule inhibitor of...

journal_title：Cancer discovery

authors： Saura C,Roda D,Roselló S,Oliveira M,Macarulla T,Pérez-Fidalgo JA,Morales-Barrera R,Sanchis-García JM,Musib L,Budha N,Zhu J,Nannini M,Chan WY,Sanabria Bohórquez SM,Meng RD,Lin K,Yan Y,Patel P,Baselga J,Tabernero J,

更新日期：2017-01-01 00:00:00