EFM19 is another ER+ cell line derived from a pleural effusion metastasis of a 50 year old Caucasian women previously diagnosed with ductal breast carcinoma. As expected, this ER+ cell line has an expression profile of a luminal lineage breast cancer. The STR profile and other genomic data sets and information pertinent to this cell line can be found here at Cellosaurus, or here at COSMIC, or here at DepMap portal.
Oncogene Signature: The Oncogene signature of this cell line is one that is somewhat common among aggressive luminal ER+ breast cancer cell lines in that it not only exhibits high level overexpression of ESR1, the cells also have a common PIK3CA mutation, and a common TP53 mutation. ESR1 and PIK3CA were both hits in both the CRISPR and RNAi functional screens, making them both essential genes. In addition to these common breast cancer oncogenes, there is copy number gain and overexpression of U2AF2 . This genomic alteration is rare in breast cancer, but it is included here because this gene was a screen hit in both the CRISPR and RNAi screens. The remaining genomic alterations listed here are unlikely to be of significance because the level of copy number gain and gene expression is relatively low, and none of the genes were hits in either functional screen. Thus, the clear drivers of this breast cancer cell line are ESR1 (ERa) and PIK3CA in the context of a TP53 mutation.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| ESR1 | -1.188959455 | -0.970855159 | 4.292021817 | 0.4591 | ||
| PIK3CA | -0.996488226 | -1.267484115 | 0.69426519 | 0.4686 | p.H1047L | 1582 |
| U2AF2 | -0.84327916 | -0.854302565 | 1.057998394 | 1.9862 | ||
| SUZ12 | -0.262446185 | -0.249356983 | 1.885184287 | 1.1043 | ||
| TP53 | -0.105642512 | -0.294114284 | 0.073192481 | -0.5448 | p.H193R | 193 |
| ROBO1 | -0.026592847 | 0.007313573 | 1.329939432 | 1.536 | ||
| MSI2 | 0.000460894 | 0.28926237 | 1.132930122 | 1.0713 | ||
| RNF43 | 0.070426435 | 0.111431235 | -1.055174803 | 1.0713 | ||
| GNAS | 0.102465802 | -0.307535306 | 1.007154739 | 1.4711 |
Signature of best druggable targets in this cell line: As one might expect for a cell line with two functional-druggable oncogenes, there are several drugs that target these genes that the cells are sensitive to. With regard to the ER-targeted drugs, the cells are highly sensitive to the SERD drug GDC0810 and moderately sensitive to the clinically available SERD drug fulvestrant. Interestingly, the cells are not particularly sensitive to the selective estrogen receptor modulator (SERM) drug Tamoxifen. This is interesting because there are some breast cancer cells that are dependent on the estrogen receptor but not dependent on estrogen itself. Thus, in such cells, the estrogen receptor signals in a ligand independent manner. Such cells would be expected to be responsive to a receptor degrader, but not sensitive to drugs that work by blocking the action of ligand on the receptor. With respect to the PIK3CA targeted drugs, once again, it is not surprising that the cells are have a low Z-score for Alpelisib, the drug that specifically targets PIK3CA. And, like other cell lines that signal through the PI3K-AKT pathway, EFM19 cells exhibit moderate sensitivity to several AKT-targeted drugs, and both AKT1 and AKT2 are expressed in these cells. Beyond these more obvious candidate targets, these cells are also highly sensitive to several drugs that target genes in the apoptosis pathway. BCL2L1 was a hit in both screens and the cells exhibit moderate sensitivity to the BCL2L1-specific drug WEHI-539. These cells are also highly sensitive to two different drugs that target XIAP and which have Z-scores less than -2.0. Thus, in this cell line there is an opportunity to combine a drug that targets either ER or PIK3CA with a drug that sensitizes cells to apoptosis, which could lead to synergistic cell killing.
| EFM19.Tier1 | ||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | |
| GDC0810 | ESR1 | 0 | -2.291865 | 0.4591 | 4.292021817 | NULL | 0 | |
| Alpelisib | PIK3CA | 0 | -1.680552 | 0.4686 | 0.69426519 | p.H1047L | 1 | |
| EFM19.Tier2 | ||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | mutation | lfc | achilles_score | demeter |
| AZD5582 | BIRC2 | 0 | -2.028933 | -0.5182 | NULL | -0.863141145 | -0.800338798 | -0.314165752 |
| MK-2206 | AKT1 | -2.203388 | -1.286501 | 0.1518 | NULL | 0.096149828 | -0.509550684 | -0.490093769 |
| MK-2206 | AKT2 | -2.203388 | -1.286501 | 0.0512 | NULL | -0.045701583 | -0.577284015 | -0.443699295 |
| AKT inhibitor VIII | AKT1 | -3.093019 | 0 | 0.1518 | NULL | 0.096149828 | -0.509550684 | -0.490093769 |
| AKT inhibitor VIII | AKT2 | -3.093019 | 0 | 0.0512 | NULL | -0.045701583 | -0.577284015 | -0.443699295 |
| EFM19.Tier3 | ||||||||
| Drug Name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | achilles_score | demeter |
| LCL161 | BIRC3 | 0.383479 | -3.680125 | -0.5182 | -0.93490322 | NULL | 0.324900281 | 0.011807655 |
| LCL161 | XIAP | 0.383479 | -3.680125 | -0.0465 | -0.17900366 | NULL | -0.119971341 | -0.075033902 |
| AZD5582 | NAIP | 0 | -2.028933 | -0.0258 | -0.9634702 | NULL | -0.172268333 | 0.076249307 |
| AZD5582 | BIRC3 | 0 | -2.028933 | -0.5182 | -0.93490322 | NULL | 0.324900281 | 0.011807655 |
| AZD5582 | XIAP | 0 | -2.028933 | -0.0465 | -0.17900366 | NULL | -0.119971341 | -0.075033902 |
