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Intermittent or Continuous Panitumumab Plus FOLFIRI for RAS/B-RAF Wild-type Metastatic Colorectal Cancer

ABSTRACT: The investigators hypothesize that intermittent first-line Panitumumab plus FOLFIRI is effective as the same regimen given continuously, in unresectable metastatic RAS and BRAF wild type colorectal cancer patients. Correlative studies on tumor and blood samples could identify potential biomarkers of efficacy and help defining personalized treatment strategy.

DISEASE(S): Colorectal Cancer Stage Iv,Colorectal Neoplasms

PROVIDER: 2342062 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Intermittent or continuous Panitumumab plus FOLFIRI for first-line treatment of patients with RAS/B-RAF wild-type metastatic colorectal cancer: a randomized phase 2 trial

Project description:Primary objectives: To investigate whether experimental intermittent treatment of Panitumumab + FOLFIRI (given until progression during treatment or cumulative toxicity) results in a Progression Free Survival on treatment (PFSOT) similar to that obtained with standard continuous treatment of Panitumumab + FOLFIRI (given until progression or cumulative toxicity). Primary endpoints: PFSot is defined as the time from randomization to the firstobjective disease progression documented in patients undergoing treatment cycle (objective disease progression during treatment free intervals are excluded) or death due to any cause, whichever occurs first.

| 2537370 | ecrin-mdr-crc

Intermittent Drug Treatment of BRAFV600E Melanoma Cells Delays Resistance by Sensitizing Cells to Rechallenge

Project description:Melanoma patients receiving drugs targeting BRAFV600E and MKK1/2 invariably develop resistance and continue progression, limiting the efficacy of treatment. As an alternative to continuous dosing schedules, intermittent treatment strategies involving intervening periods of drug withdrawal have been proposed to delay resistance. The efficacy of this treatment strategy has been supported by preclinical findings and several clinical case reports. The beneficial effect of intermittent treatment has been attributed to “drug addiction”, in which the cell viability of resistant cells is compromised during periods of drug removal, presumably due to MAPK pathway hyperactivation. However, the cellular and molecular responses to intermittent treatment are still incompletely understood. Here, we investigate effects of intermittent treatment with the BRAFV600E inhibitor, encorafenib, in a metastatic melanoma cell line engineered to express genes conferring resistance to BRAF inhibition. We show that intermittent treatment shows superior growth suppression compared to continuous treatment for resistant cells that substantially reactivate the MAPK pathway. While drug addiction is clearly observable in these cells, it fails to account for the advantageous effects of intermittent treatment. Instead, growth suppression can mainly be explained by resensitization as most cell death is observed upon readdition of drug following periods of drug removal. Gene expression analysis shows that a unique and reversible transcriptional state is induced in intermittently treated cells following periods of drug removal. Thus, we conclude that the beneficial effects of intermittent treatment in our model are best explained by adaptive, non-mutational changes in transcription which confer drug resensitization.

2018-12-01 | GSE117123 | GEO

Intermittent Hypoxia ageing

Project description:Expression data from mice exposed to intermittent hypoxia and mice reared for 12 months. We used microarrays to analyze the transcriptome of hippocampus from mice exposed to intermittent hypoxia or aged mice.

2016-12-27 | GSE62385 | GEO

RNA expression profiling of subcutaneous adipose tissue before and after dietary intervention with intermittent or continuous calorie restriction

Project description:Obesity, a major risk factor for chronic diseases, is related to dsyfunctional adipose tissue signaling. First human trials suggest benefits of intermittent calorie restriction diet (ICR) in chronic disease prevention that may exceed those of continuous calorie restriction diet (CCR), even at equal net calorie intake. The effect of intermittent calorie restriction on adipose tissue signaling has not been investigated to date. Thus we initiated a randomized controlled trial to analyze the effect of ICR (eu-caloric diet on five days and two days per week with energy restriction of 75%), CCR (daily energy restriction of 20%) and a control group on subcutaneous adipose tissue (SAT) gene expression. 150 overweight or obese non-smoking adults (50 per group, 50% women) were randomly asiged to one of the study arms. SAT biopsies were taken before and after the 12 week intervention phase.

2019-03-01 | E-MTAB-5926 | biostudies-arrayexpress

Transcription profiling of mouse primary osteoblastic cells after intermittent of continuous treatment with parathyroid hormone to investigate the role of beta-arrestin2

Project description:Role of beta-arrestin2 in response to intermittent or continuous parathyroid hormone (PTH) treatment.

2009-07-20 | E-TABM-624 | biostudies-arrayexpress

Intermittent Hypoxia ageing

Project description:Intermittent Hypoxia ageing

| PRJNA263964 | ENA

Transcriptome analysis of mouse heart under different intermittent fasting conditions

Project description:Various intermittent fasting regimes are popularly being practiced but the scientific understanding for the mechanisms of intermittent fasting remains unclear. Observing the overall transcriptomic changes in specific organs, including heart, may contribute substantially in understanding the diverse effects of intermittent fasting. Our current study further investigate the differential transcriptomic changes in the heart among the different regimes of intermittent fasting as well.

2023-09-27 | GSE133290 | GEO

Intermittent fasting alters the spatiotemporal atlas of transcriptomes

Project description:Transcription factors may orchestrate the health benefits of intermittent fasting through directing the expression of genome. Here, we find intermittent fasting can spin the spatiotemporal profile of transcription factors, and provide an atlas of transcription factors in biological space, time and feeding regimen.

2022-10-27 | GSE154797 | GEO

Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke

Project description:Intermittent fasting is previously reported to exhibit neuroprotection against experimental ischemic stroke. However, the detailed understanding of protection mechanisms are lacking. By observing the overall transcriptomic changes in each timepoint of ischemic stroke would benefit the understanding of underlying active pathways and mechanisms. Here, we conduct experimental MCAO ischemic stroke on mice exposed to different daily intermittent fasting method to compare not only among the ischemic stroke timepoints but also the efficacy of different intermittent fasting interventions. Our current study presented the transcriptomic changes for the first time in specific timepoints of ischemic stroke as well as under the condition of intermittent fasting. A number of neuroprotective mechanisms-related genes were significantly affected by intermittent fasting conditions in differential manners.

2018-07-11 | GSE116878 | GEO

Expression data from rat soleus during chronic intermittent physical inactivity

Project description:Global gene expression of the rat soleus muscle was assessed with microarrays after 11 days of intermittent physical inactivity (10 hr/day) and compared to normally caged rats with voluntary standing and intermittent cage movements. Keywords: between group design

2006-07-04 | GSE5217 | GEO

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