The MDA-MB-468 breast cancer cell line is an ER-negative, HER2 negative cell line that is perhaps best known for it’s amplification and overexpression of the EGFR gene, which is rare in breast cancer specimens and cell lines. the MDA-468 cell line was derived from the pleural effusion metastasis of a 51 year old female of mostly African ancestry (80%) and 20% European ancestry. the cell line has been classified as a Basal A breast cancer cell line. The STR profile along with other genomic data and information pertinent to this cell line can be found here at Cellosaurus, or here at COSMIC, or here at DepMap portal.
Oncogene Signature: This oncogene signature shows the high level amplification and overexpression of EGFR in these cells, and also shows that this gene was not a hit in either functional screen. As will be discussed elsewhere, this finding is in keeping with the relative insensitivity of these cells to EGFR targeted drugs. Thus, the EGFR amplification in breast cancer does not behave in a manner similar to the HER2 amplification. It is also interesting and consistent with other breast cancer cells in which EGFR signaling appears to be important that the cells also have a PTEN mutation, and this genomic interaction could be important for these cells. And like most basal type breast cancers, these cells have a TP53 mutation. In that regard, it is very interesting that none of the putative dominantly acting oncogenes that are genomically altered were hits in this cell line.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| EGFR | 0.162481991 | -0.180457678 | 5.55950475 | 4.8257 | ||
| KEAP1 | -0.302221628 | -0.248520978 | 1.830308407 | 1.7933 | ||
| DNMT1 | -0.106170792 | -0.214516302 | 2.197406933 | 1.7933 | ||
| TYK2 | 0.066281851 | -0.153737669 | 1.836706063 | 1.7933 | ||
| LMO2 | -0.00237731 | 0.021348075 | 1.818324813 | 1.4201 | ||
| WT1 | 0.233358309 | 0.003901533 | 3.271044453 | 1.4201 | ||
| YES1 | 0.025638939 | -0.199924688 | 1.791816215 | 1.164 | ||
| PTPN2 | 0.438807227 | 0.196531317 | 1.800864466 | 1.1269 | ||
| RRAGC | 0.077430985 | 0.032194807 | 1.230156819 | 1.1022 | ||
| PTEN | 0.415855335 | -0.05649151 | -0.153870256 | 0.1976 | NA | 42 |
| TP53 | 0.067648145 | -0.374508228 | 1.410795929 | -0.4279 | p.R273H | 669 |
MDA-468 drug sensitivities. The single Tier 1 drug for this cell line is the monoclonal antibody drug Cetuximab, which targets EGFR. Interestingly, these cells are not sensitive to ether EGFR tyrosine kinase inhibitors gefitinb or erlotinib. This patter of drug sensitivity associated with EGFR amplification is exactly what is observed in BT20 breast cancer cells. Tier 2 contains a list of several drugs in which sensitivity was associated with essentiality in one or both of the screens. Several of these drugs target AURKA and/or AURKB which were screen hits, suggesting that this is true on-target drug sensitivity. The cells are also highly sensitive to two pan-specific drugs that target FLT3, KIT, and PDGFR and the redundancy of the sensitivity to these drugs is strongly supportive of a true on-target effect, though based on screen data and expression data, it’s not possible to determine which is the most important target of this drug. Finally, the cells are sensitive to a drug that targets two BRD gene family members both of which are expressed in the cells.
| MDA-468 T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| Cetuximab | EGFR | -2.75783 | 0 | 4.8257 | 5.55950475 | NULL | 0 | ||
| MDA-468T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| Alisertib | AURKA | -2.465899 | -1.913495 | 0.1355 | 0.539144117 | NULL | 0 | -1.506589358 | -0.265911257 |
| ZM447439 | AURKA | -0.44177 | -1.755754 | 0.1355 | 0.539144117 | NULL | 0 | -1.506589358 | -0.265911257 |
| ZM447439 | AURKB | -0.44177 | -1.755754 | -0.4279 | 0.0761734 | NULL | 0 | -1.462115073 | -1.113029796 |
| Tozasertib | AURKA | 0 | -1.736552 | 0.1355 | 0.539144117 | NULL | 0 | -1.506589358 | -0.265911257 |
| Tozasertib | AURKB | 0 | -1.736552 | -0.4279 | 0.0761734 | NULL | 0 | -1.462115073 | -1.113029796 |
| RO-3306 | CDK1 | -2.560515 | -1.651933 | 0.1226 | 0.427439126 | NULL | 0 | -1.783887068 | -0.975722452 |
| Mirin | MRE11 | -0.971963 | -1.64859 | -0.3597 | -0.528598364 | NULL | 0 | -0.878190662 | -0.142376606 |
| MIM1 | MCL1 | -2.003202 | -0.739023 | 0.3336 | 0.443468884 | NULL | 0 | -0.972956818 | -0.079361639 |
| GSK1070916 | AURKA | -2.640992 | 0 | 0.1355 | 0.539144117 | NULL | 0 | -1.506589358 | -0.265911257 |
| MDA-468 T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| Axitinib | KDR | -0.947078 | -2.223161 | -0.4688 | 0.783376059 | NULL | 0 | -0.008905027 | 0.091534452 |
| Axitinib | KIT | -0.947078 | -2.223161 | -0.4688 | 0.582739634 | NULL | 0 | -0.199518644 | 0.01432588 |
| Axitinib | PDGFRA | -0.947078 | -2.223161 | -0.4688 | 0.153350777 | NULL | 0 | -0.125567475 | 0.023855018 |
| Axitinib | PDGFRB | -0.947078 | -2.223161 | -0.0199 | -0.090602549 | NULL | 0 | 0.041319053 | -0.06914795 |
| OF-1 | BRD1 | 0 | -2.162295 | 0.1339 | 0.023448655 | NULL | 0 | -0.19213429 | -0.038047523 |
| OF-1 | BRPF1 | 0 | -2.162295 | -0.438 | -0.23298659 | NULL | 0 | -0.076208349 | 0.071575345 |
| Alisertib | AURKA | -2.465899 | -1.913495 | 0.1355 | 0.539144117 | NULL | 0 | -1.506589358 | -0.265911257 |
| LGK974 | PORCN | -1.377632 | -1.786381 | -0.301 | 0.082800305 | NULL | 0 | 0.125476673 | 0.066037336 |
| Wnt-C59 | PORCN | -1.838391 | -1.78048 | -0.301 | 0.082800305 | NULL | 0 | 0.125476673 | 0.066037336 |
| MN-64 | TNKS | 0 | -1.779605 | -0.329 | 0.054209048 | NULL | 0 | 0.027411518 | -0.127474407 |
| MN-64 | TNKS2 | 0 | -1.779605 | 0.1976 | 0.429874827 | NULL | 0 | -0.164077025 | -0.150333091 |
| ZM447439 | AURKA | -0.44177 | -1.755754 | 0.1355 | 0.539144117 | NULL | 0 | -1.506589358 | -0.265911257 |
| ML323 | USP1 | 0 | -1.744507 | 0.5616 | 1.200568537 | NULL | 0 | -0.144738233 | -0.002211854 |
| ML323 | WDR48 | 0 | -1.744507 | -0.4151 | -0.478131617 | NULL | 0 | -0.467539286 | -0.017768334 |
| Tozasertib | AURKA | 0 | -1.736552 | 0.1355 | 0.539144117 | NULL | 0 | -1.506589358 | -0.265911257 |
| Tozasertib | AURKC | 0 | -1.736552 | 0.4458 | 1.24506046 | NULL | 0 | 0.000925925 | 0.062100238 |
| PCI-34051 | HDAC1 | 0 | -1.702482 | 0.5358 | 0.547494586 | NULL | 0 | -0.201059589 | -0.023783179 |
| PCI-34051 | HDAC6 | 0 | -1.702482 | -0.301 | 0.754188409 | NULL | 0 | 0.155155593 | -0.057835481 |
| PCI-34051 | HDAC8 | 0 | -1.702482 | -0.2529 | 0.85944357 | NULL | 0 | -0.283946739 | -0.071352342 |
| GSK1904529A | IGF1R | -1.982991 | -1.651198 | -0.4331 | -1.031405533 | NULL | 0 | 0.048088073 | 0.037719659 |
| GSK1904529A | INSR | -1.982991 | -1.651198 | -0.4231 | 0.371754969 | NULL | 0 | 0.045668635 | 0.121119677 |
| GSK1070916 | AURKA | -2.640992 | 0 | 0.1355 | 0.539144117 | NULL | 0 | -1.506589358 | -0.265911257 |
| GSK1070916 | AURKC | -2.640992 | 0 | 0.4458 | 1.24506046 | NULL | 0 | 0.000925925 | 0.062100238 |
| Amuvatinib | FLT3 | -2.2053 | 0 | -0.3704 | 0.527247003 | NULL | 0 | -0.496559756 | 0.107465617 |
| Amuvatinib | KIT | -2.2053 | 0 | -0.4688 | 0.582739634 | NULL | 0 | -0.199518644 | 0.01432588 |
| Amuvatinib | PDGFRA | -2.2053 | 0 | -0.4688 | 0.153350777 | NULL | 0 | -0.125567475 | 0.023855018 |
| Doramapimod | MAPK14 | -1.970774 | 0.498304 | 0.4974 | 0.49737337 | NULL | 0 | -0.213664279 | 0.076970122 |
| Doramapimod | MAPK9 | -1.970774 | 0.498304 | 0.4668 | 0.794127574 | NULL | 0 | 0.356826997 | 0.050990165 |
