Darwin OncoTarget™/OncoTreat™

The DarwinOncoTarget™ and DarwinOncoTreat™ tests analyze whole transcriptome sequencing (RNASeq) of a patient-derived tumor sample to identify aberrantly activated proteins for which a clinically-relevant targeted inhibitor already exists and to match tumor-specific dependencies with clinically-relevant drugs, respectively.  By clinically-relevant we mean FDA approved drugs as well as investigational drugs in Phase 2 and 3 clinical trials. More specifically, the  DarwinOncoTarget™  test currently assesses aberrant activity of 193 proteins that can be targeted by 94 FDA approved oncology drugs, and by 239 investigational oncology agents. These numbers will change as more information becomes available.  The DarwinOncoTreat™ test first identifies tumor-checkpoints comprising master regulator proteins that represent critical tumor dependencies; this is accomplished by assessing the concerted activity of 6,293 regulatory proteins. It then prioritizes drugs based on their experimentally tested ability to revert the activity of the tumor checkpoint in appropriate cell line models. While DarwinOncoTarget™ is available for all human malignancies, DarwinOncoTreat™ is currently available only for specific tumor subtypes for which the experimental assessment has already been completed (currently, breast carcinoma, glioblastoma multiforme, meningioma, neuroendocrine tumors, and sarcomas). Additional tumor subtypes will be added as the experimental validation data becomes available.

For patients with advanced cancers who have failed standard therapy these results may help the oncologist prioritize potential drug targets or select clinical trials.

1. Frozen sections of tumor. Serial H&E-stained sections should show at least 50% tumor as estimated by pathologist review of the tumor block. Ten 10-micrometer sections (approximately 50mg of tissue) should be collected in a 1.5ml or 2ml DNAse, RNAse free microcentrifuge tube and delivered to the laboratory on dry ice.  If sections do not contain an area of at least 50% tumor, then an area of tumor will be marked on the slide and the block trimmed to select for an area of at least 50% tumor.
2. Paraffin embedded sections of tumor: Serial H&E-stained sections should show at least 50% tumor as estimated by pathologist review of the tumor block. Ten 10-micrometer sections (approximately 50 mg of tissue) should be collected in a 1.5ml or 2 ml DNAse, RNAse free microcentrifuge tube and delivered to the laboratory at room temperature. If the sections contains less than 50% tumor, submit 10 unstained slides with an adjacent H&E section. It should be possible to circle an area of at least 50% tumor for macrodissection.
3. Leukemia samples: Whole blood or white blood cells, with lesional cells constituting at least 50% of nucleated cells, delivered to the lab at room temperature within 24 hours of collection (in an EDTA tube, or RPMI). EDTA blood tubes should be filled to capacity (2ml or 7ml). At least 0.5ml of cellular marrow, or at least a million cells.
4. RNA from tumor. For tumor a serial section should show an acceptable percentage of tumor, or there should be notation from a qualified pathologist that the specimen contains at least 50% tumor. (Note: for liquid samples, the specimen should be accompanied by a flow cytometry report or cytology report indicating a predominance of tumor cells in the sample). Transport to the laboratory on dry ice (-70C)