Opendata, web and dolomites
2MoveMate4Melanoma
A treatment for BRAF inhibitor resistant melanoma
Total Cost €
0EC-Contrib. €
0Partnership
0Views
02MoveMate4Melanoma project word cloud
Explore the words cloud of the 2MoveMate4Melanoma project. It provides you a very rough idea of what is the project "2MoveMate4Melanoma" about.
validate
tumors
map
melanoma
invariably
hyperactivation
histone
mek
cellular
brafi
mutant
causing
chronic
durable
grant
evaluable
proof
least
diagnosed
inhibitors
laboratory
inhibitor
benefit
performed
urgent
almost
braf
regression
subsequent
leads
death
limits
mutations
therapy
strategies
drugs
deacetylase
activating
persistent
treat
melanomas
drug
clinical
tumor
treatments
signaling
progression
proliferation
explaining
activation
effect
gene
perform
shown
sequential
proven
metastatic
highlights
temporary
translational
human
annually
either
initial
ultimately
arrest
withdrawal
holiday
biopsies
50
treatment
complete
patients
erc
secondary
resistant
hdaci
combination
alone
cell
resistance
always
kinase
re
found
free
some
mice
survival
consequence
transient
Project "2MoveMate4Melanoma" data sheet
The following table provides information about the project.
| Coordinator |
STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Total cost | 149˙750 € |
| EC max contribution | 149˙750 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2015-PoC |
| Funding Scheme | ERC-POC |
| Starting year | 2016 |
| Duration (year-month-day) | from 2016-05-01 to 2017-10-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS | NL (AMSTERDAM) | coordinator | 149˙750.00 |
Map
Project objective
Some 50% of human melanoma tumors have activating mutations in the BRAF gene. BRAF inhibitor drugs given either alone or in combination with MEK inhibitors have improved progression-free and overall survival in patients with BRAF mutant metastatic melanoma. However, drug resistance invariably limits the duration of clinical benefit of such treatments and is almost always associated with re-activation of signaling through the MAP kinase pathway in the presence of drug due to secondary mutations in the pathway. This highlights the urgent need to develop strategies to treat melanomas that have developed resistance to BRAF and/or MEK inhibitors. As part of an ERC advanced grant, my laboratory has shown that BRAF inhibitor withdrawal in melanomas that have developed resistance to BRAF inhibitors leads to a transient growth arrest that is the consequence of temporary hyperactivation of signaling through the MAP kinase pathway, explaining the so called “drug holiday effect”. We have also found that subsequent treatment of such BRAF inhibitor resistant melanomas with Histone DeACetylase inhibitor drugs (HDACi) leads to persistent hyperactivation of MAP kinase signaling, causing both chronic proliferation arrest and cell death, ultimately leading to complete regression of BRAF-inhibitor resistant melanomas in mice. We propose here to perform a proof of concept study in at least 10 evaluable melanoma patients that, after proven initial tumor response, have developed resistance to BRAF inhibitors to validate that subsequent treatment of such patients with an HDACi drug will result in durable responses. Translational studies on tumor biopsies taken before, during and after HDACi treatment will be performed to study the cellular effects of HDACi treatment. Our goal is to provide initial proof of concept in patients for use of this sequential BRAFi-HDACi therapy as the treatment of choice for the some 40,000 BRAF mutant melanomas that are diagnosed in the EU annually.
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The information about "2MOVEMATE4MELANOMA" are provided by the European Opendata Portal: CORDIS opendata.
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