UNASSIGNED: Metastatic @entity14 (mCRC) carries a poor prognosis with an overall 5-year survival of 13.1%. Therapies guided by @entity5 profiling have suggested benefit in advanced @entity5 . We used a multiplatform molecular profiling (MP) approach to identify key molecular changes that may provide therapeutic options not typically considered in mCRC. We evaluated 6892 mCRC referred to Caris Life Sciences by MP including sequencing (Sanger/NGS), immunohistochemistry (IHC) and in-situ hybridization (ISH). mCRC metastases to liver, brain, ovary or lung (n=1507) showed differential expression of markers including high protein expression of TOPO1 (52%) and/or low @entity4736 (57%), @entity1950 (71%) and @entity8724 (39%), suggesting possible benefit from @entity2600 , @entity136 , @entity1487 / @entity416 and @entity2903 , respectively. Lung metastases harbored a higher @entity1722 protein expression than the primary @entity694 (4% vs. 1.8%, p=0.028). Brain and lung metastases had higher @entity984 mutations than other sites (65% vs 59% vs 47%, respectively, p=0.07, <0.01), suggesting poor response to anti- @entity470 therapies. @entity817 -mutated @entity14 (n=455) showed coincident high protein expression of @entity4736 (56%), @entity1950 (53%) and low @entity3820 (22%) as compared with @entity817 wild-type @entity5 . @entity984 -mutated mCRC had higher protein expression of @entity1916 (47% vs. 36%) and lower @entity8724 (56% vs. 63%), suggesting consideration of @entity1916 inhibitors and @entity2903 . @entity984 -mutated @entity14 had high @entity537 (42% vs. 33%) and low @entity1722 by IHC (0.5%) and @entity1722 by FISH (3%, p <0.05). @entity14 primaries had a lower incidence of @entity10160 and @entity817 mutations in @entity5 versus @entity694 (10% and 3.3%, respectively). MP of 6892 CRCs identified significant differences between primary and metastatic sites and among @entity817 / @entity984 sub-types. Our findings are hypothesis generating and need to be examined in prospective studies. Specific therapies may be considered for different actionable targets in mCRC as revealed by MP.

Molecular profiling of 6,892 XXXX samples suggests different possible treatment options specific to metastatic sites.

@entity4736 :: ('6240', 'Gene') :: ['RRM1'] @entity2600 :: ('MESH:C051890', 'Chemical') :: ['irinotecan'] @entity416 :: ('MESH:C110904', 'Chemical') :: ['capecitabine'] @entity10160 :: ('5290', 'Gene') :: ['PIK3CA'] @entity1722 :: ('2064', 'Gene') :: ['Her2', 'HER2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'rectal cancer', 'tumors'] @entity984 :: ('3845', 'Gene') :: ['KRAS'] @entity470 :: ('1956', 'Gene') :: ['EGFR'] @entity8724 :: ('4255', 'Gene') :: ['MGMT'] @entity3820 :: ('5159', 'Gene') :: ['PDGFR'] @entity537 :: ('10381', 'Gene') :: ['TUBB3'] @entity1916 :: ('4233', 'Gene') :: ['c-MET'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer', 'CRC'] @entity2903 :: ('MESH:C047246', 'Chemical') :: ['temozolomide'] @entity1950 :: ('MESH:C536962', 'Disease') :: ['TS'] @entity817 :: ('673', 'Gene') :: ['BRAF'] @entity694 :: ('MESH:D003110', 'Disease') :: ['colon tumors', 'colon cancer'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['gemcitabine'] @entity1487 :: ('MESH:D005472', 'Chemical') :: ['5FU']
@entity14 :: (MESH:D015179,Disease) :: ['colorectal cancer']
