| Title |
Rational development of synergistic combinations of chemotherapy and molecular targeted agents for colorectal cancer treatment
|
|---|---|
| Published in |
BMC Cancer, August 2018
|
| DOI | 10.1186/s12885-018-4712-z |
| Pubmed ID | |
| Authors |
Diego Tosi, Esther Pérez-Gracia, Salima Atis, Nadia Vié, Eve Combès, Mélissa Gabanou, Christel Larbouret, Marta Jarlier, Caroline Mollevi, Adeline Torro, Maguy Del Rio, Pierre Martineau, Céline Gongora |
| Abstract |
The irinotecan-induced phosphokinome changes in colorectal cancer (CRC) cells were used to guide the selection of targeted agents to be tested in combination with irinotecan. Phosphokinome profiling with peptide arrays of tumour samples from nude mice xenografted with HT29 cells and treated or not with an effective dose of irinotecan was used to identify signalling pathways activated by irinotecan treatment. Then, drugs targeting these pathways were combined in vitro with irinotecan to test potential synergistic effect. The interactions between these drug combinations were assessed by a dose matrix approach. Confirmation of the most potential combination has been confirmed in vivo in xenografted mice. Irinotecan induced in vivo the activation of AKT and MEK1 phosphorylation. The dose matrix approach showed that BKM120 (PI3K inhibitor) and MEK162 (MEK inhibitor) are synergistic in vitro and in vivo with a cytostatic and cytotoxic effect, while combination of BKM120 and irinotecan or MEK162 and irinotecan are only additive or even antagonistic. However, the triple combination of SN38, BKM120 and MEK162 showed a better synergistic effect that BKM120 and MEK162, indicating that the cells need to inhibit both AKT and ERK pathways to become more sensitive to irinotecan-based chemotherapies. Analysis of chemotherapy-induced phosphokinome changes helps to elucidate the mechanisms of drug resistance and to guide the selection of targets for combination therapies with synergistic activity. |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 38 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 24% |
| Student > Bachelor | 5 | 13% |
| Researcher | 4 | 11% |
| Student > Postgraduate | 3 | 8% |
| Student > Master | 3 | 8% |
| Other | 1 | 3% |
| Unknown | 13 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 21% |
| Biochemistry, Genetics and Molecular Biology | 7 | 18% |
| Engineering | 3 | 8% |
| Agricultural and Biological Sciences | 3 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
| Other | 2 | 5% |
| Unknown | 13 | 34% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 August 2018.
All research outputs
#4,243,439
of 23,100,534 outputs
Outputs from BMC Cancer
#1,023
of 8,385 outputs
Outputs of similar age
#82,091
of 330,840 outputs
Outputs of similar age from BMC Cancer
#17
of 136 outputs
Altmetric has tracked 23,100,534 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 8,385 research outputs from this source. They receive a mean Attention Score of 4.3. This one has done well, scoring higher than 86% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 330,840 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.
We're also able to compare this research output to 136 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 86% of its contemporaries.