Preliminary results from a phase II trial of tipifarnib in squamous cell carcinomas (SCCs) with HRAS mutations

Published on Oct 1, 2018in Annals of Oncology18.274
· DOI :10.1093/ANNONC/MDY287.002
Alan Loh Ho10
Estimated H-index: 10
(MSK: Memorial Sloan Kettering Cancer Center),
Nicole G. Chau21
Estimated H-index: 21
(Harvard University)
+ 14 AuthorsA. Gualberto3
Estimated H-index: 3
Sources
Abstract
📖 Papers frequently viewed together
4 Citations
26 Citations
18 Authors (Deyin Xing, ..., Wei Song)
4 Citations
References0
Newest
Cited By14
Newest
#2Pantelis A. NicolaH-Index: 1
Last. Colin R LindsayH-Index: 19
view all 4 authors...
KRAS is one of the most common human oncogenes, but concerted efforts to produce direct inhibitors have largely failed, earning KRAS the title of “undruggable”. Recent efforts to produce subtype specific inhibitors have been more successful, and several KRASG12C inhibitors have reached clinical trials, including adagrasib and sotorasib, which have shown early evidence of efficacy in patients. Lessons from other inhibitors of the RAS pathway suggest that the effect of these drugs will be limited ...
1 CitationsSource
#1Tomohiro Kondo (Kyoto University)H-Index: 7
#2Junichi Matsubara (Kyoto University)H-Index: 16
Last. Manabu Muto (Kyoto University)H-Index: 61
view all 21 authors...
Comprehensive genomic profiling (CGP) testing by next-generation sequencing has been introduced into clinical practice as part of precision cancer medicine to select effective targeted therapies. However, whether CGP testing at the time of first-line chemotherapy could be clinically useful is not clear. We conducted this single-center, prospective, observational study to investigate the feasibility of CGP testing for chemotherapy-naive patients with stage III/IV gastrointestinal cancer, rare can...
Source
#1Catherine A. Hurd (University of Cambridge)H-Index: 2
#2Helen R. Mott (University of Cambridge)H-Index: 27
Last. Darerca Owen (University of Cambridge)H-Index: 17
view all 3 authors...
1 CitationsSource
#1Mara Gilardi (UCSD: University of California, San Diego)H-Index: 11
#2Zhiyong Wang (UCSD: University of California, San Diego)H-Index: 24
Last. Francis BurrowsH-Index: 29
view all 14 authors...
Tipifarnib is a potent and highly selective inhibitor of farnesyltransferase (FT). FT catalyzes the post-translational attachment of farnesyl groups to signaling proteins that are required for localization to cell membranes. Although all RAS isoforms are FT substrates, only HRAS is exclusively dependent upon farnesylation, raising the possibility that HRAS mutant tumors might be susceptible to tipifarnib-mediated inhibition of FT. Here, we report the characterization of tipifarnib activity in a ...
8 CitationsSource
#1Glenn J. Hanna (Harvard University)H-Index: 17
#2Jeffrey P. Guenette (Brigham and Women's Hospital)H-Index: 10
Last. Alan L. Ho (Cornell University)H-Index: 36
view all 15 authors...
BACKGROUND To the authors' knowledge, there are no approved therapies for recurrent, metastatic (R/M) salivary gland carcinoma (SGC), but molecularly targeted therapies warrant ongoing investigation. In the current study, the authors have reported on the efficacy of tipifarnib in patients with aggressive HRAS-mutant, R/M SGC. METHODS The current prospective, nonrandomized, multicenter, international cohort study involved 8 centers and was conducted from May 2015 to June 2019. The median follow-u...
2 CitationsSource
#1Andrea NecchiH-Index: 35
#2Russell MadisonH-Index: 12
Last. Siraj M. AliH-Index: 65
view all 12 authors...
Abstract Background Characterization of the different genomic alterations (GAs) in urothelial carcinoma (UC), by site of origin, may identify contrasting therapeutic opportunities and inform distinct putative pathogenetic mechanisms. Objective To describe the genomic landscape of UC based on the anatomic site of the primary tumor. Design, setting, and participants In total, 479 upper tract UC (UTUC) and 1984 bladder UC (BUC) patients underwent comprehensive genomic profiling (CGP) to evaluate al...
6 CitationsSource
#1Lisa M. Butler (University of Adelaide)H-Index: 52
#2Ylenia Perone (Imperial College London)H-Index: 8
Last. Johannes V. Swinnen (Katholieke Universiteit Leuven)H-Index: 64
view all 9 authors...
Abstract With the advent of effective tools to study lipids, including mass spectrometry-based lipidomics, lipids are emerging as central players in cancer biology. Lipids function as essential building blocks for membranes, serve as fuel to drive energy-demanding processes and play a key role as signaling molecules and as regulators of numerous cellular functions. Not unexpectedly, cancer cells, as well as other cell types in the tumor microenvironment, exploit various ways to acquire lipids an...
17 CitationsSource
Abstract Molecular profiling provides the insight that specific genetic alterations can be detected across a wide range of different histologically characterised tumour types. Thus, the basic concept of basket trials (BTs) to target those genetic alterations with the same anti-tumour agents independent of the underlying tumour type was tumour agnostic. BTs can be divided into tumour gnostic, tumour semi-gnostic, and tumour agnostic trials which cover BTs of the conventional and the complex multi...
Source
#1V. Dunnett-Kane (University of Manchester)H-Index: 1
#2E. Burkitt-Wright (University of Manchester)H-Index: 1
Last. Colin R Lindsay (University of Manchester)H-Index: 19
view all 6 authors...
Abstract Somatic mutations in RAS and related pathway genes such as NF1 have been strongly implicated in the development of cancer whilst also being implicated in a diverse group of developmental disorders named the “RASopathies”; including Neurofibromatosis 1 (NF1), Noonan syndrome (NS), Noonan syndrome with multiple lentigines (NSML), Costello syndrome (CS), cardio-facio-cutaneous syndrome (CFC), and capillary malformation-arteriovenous syndrome (CM-AVM). It remains unclear why i) there is lit...
6 CitationsSource
#1Rachel Galot (Cliniques Universitaires Saint-Luc)H-Index: 4
#1Rachel Galot (UCL: Université catholique de Louvain)H-Index: 1
Last. Jean-Pascal Machiels (UCL: Université catholique de Louvain)H-Index: 58
view all 2 authors...
Abstract Liquid biopsies (LB) are emerging in the oncology field, with promising data as new diagnostic, prognostic and treatment-monitoring tools. Squamous cell carcinoma of the head and neck (SCCHN) is a heterogenous disease and many challenges remain to improve patient outcomes. Liquid biopsy could be of interest at different stages of SCCHN disease, including better screening to diagnose more patients at an early stage, early detection of relapse after curative treatment, and the implementat...
7 CitationsSource