The aim of this proposal is to test this concept using organoid cultures and biobanked material of colon cancer patients and use these cultures to develop novel therapies in particular for the CMS4 subtype, which has mesenchymal features, a dismal…
ID
Source
Brief title
Condition
- Gastrointestinal conditions NEC
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary research question is to evaluate the association and predictive value
of sensitivity or resistance to chemotherapy of established primary human
organoids and the response of patients to the same chemotherapy. In other
words, what is the correlation between non-responsiveness of the organoids to a
specific compound and recurrence of the disease in adjuvantly treated patients.
Secondary outcome
Secondary research questions include 1) association between non-responsiveness
of the primary cultures and overall survival (OS) and disease free survival
(DFS) 2) analysis of the success rate of establishment of colon organoids
derived from patient material in a standardized clinical setting 3) We will
further explore new intervention approaches that are effectively targeting the
distinct subtypes, which will be carried forward into a spectrum of in vitro
and in vivo models in order to develop these therapies for future use 4) In
addition we will try to define the role of distinct mutations and the
regulation of EMT mesenchymal features in colon cancer and to identify key
players in this process in order to identify resistance mechanisms that play a
role in this subgroup of cancers.
Background summary
Colon cancer is currently the leading cancer type in the Netherlands. When
dealing with non-metastatic disease, the main problem is that it remains
enigmatic which patients will develop a recurrence after successful resection
of the primary cancer. This makes selection for adjuvant therapy an impossible
yet essential objective. If anything, population-based CRC screening will
intensify this dilemma as it will increase early stage diagnoses. On top of
this current adjuvant therapy is curative only in part of the patients and
therefore in urgent need of optimization. Using unbiased gene expression-based
stratification, we and others have defined 4 consensus molecular subtypes with
highly distinct biological and clinical traits, which suggests that colon
cancer should no longer be considered and treated as a homogeneous disease.
Study objective
The aim of this proposal is to test this concept using organoid cultures and
biobanked material of colon cancer patients and use these cultures to develop
novel therapies in particular for the CMS4 subtype, which has mesenchymal
features, a dismal prognosis and a reportedly poor response to therapy.
Study design
After informed consent, blood, tumor and normal tissue (FFPE and frozen) will
be stored into a biobank. A portion of the CRC material will first be cultured
before storing. Finally a drug screen will be performed on the collected
material.
Study burden and risks
Since this study is a biobanking effort, there basically is no burden or risk
associated with participation. Course of treatment will not be influenced by
participation in this study. Only in case of colonoscopy patients may be asked
for additional biopsies. This gives an almost neglectable potential additional
risk of bleeds. Also patients may be asked for blood samples, preferentially
when patients already undergo blood withdrawal.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1) (pre-stage) colorectal carcinoma 2) age of 18 or higher 3) scheduled for resection or colonoscopy 4) written informed consent for study participation
Exclusion criteria
None
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL59811.018.16 |