Table 2.

Actionability of lesions identified in at least three post-NAC specimens

Gene symbol# AlteredCategoryPotential therapy
TP5373DPrognostic (poor, potentially sensitive to WEE1 inhibitors, e.g., MK1775)
MCL140CResistance to anti-tubulins, e.g., paclitaxel, MCL1 inhibitor in development
MYC24CAurora kinase inhibitors, e.g., MLN8237, AMG 900; possible sensitivity to CDK inhibitors
PIK3CA13BPI3K/mTOR inhibitors, e.g., everolimus, temsirolimus, and others
PTEN12BPI3K/mTOR inhibitors, e.g., GSK2636771, everolimus, temsirolimus, and others
BRCA19BPARP inhibitors, e.g., olaparib, CEP-9722, rucaparib, and others
RB19DPrognostic
JAK28DJAK2 inhibitors, e.g., ruxolitinib, and others
ERBB27AHerceptin, lapatinib, and others
CDKN2A/B7ECDK4/6 inhibitors, e.g., PD0332991, LEE011, P276-00
NF15CMAPK/PI3K/mTOR inhibitors, e.g., MSC1936369B, everolimus, temsirolimus, and others
AKT35CAKT inhibitors, e.g., MK2206, PI3K/mTOR inhibitors, e.g., everolimus, temsirolimus
KRAS5AResistance to cetuximab, MEK inhibitors, e.g., MEK162
CCND15CCDK4/6 inhibitors, e.g., PD0332991, LEE011, P276-00
CCND34CCDK inhibitors, kinetin riboside
CCNE14CCDK2/4/6 inhibitors, e.g., ABT-888, PD0332991, LEE011, P276-00
CCND24CCDK inhibitors, kinetin riboside
CDK64CCDK4/6 inhibitors, e.g., PD0332991, LEE011, P276-00
IGF1R4CIGF-IR inhibitors, e.g., AMG-479, BMS-754808, MK-0646, IMC A12, and others
LRP1B3EBiologically relevant, presently no known targeted therapies
PIK3R13CPI3K pathway inhibitors
ATM3CPARP inhibitors, e.g., olaparib, CEP-9722, rucaparib
BRCA23BPARP inhibitors, e.g., olaparib, CEP-9722, rucaparib, and others
EGFR3ACetuximab, panitumumab, and others
FBXW73CResistance to anti-tubulins, potential sensitivity to PI3K/mTOR inhibitors
CDK43CCDK4/6 inhibitors, e.g., PD0332991, LEE011, P276-00
RPTOR3EBiologically relevant, possible sensitivity to mTORC1 and mTORC2 inhibitors

Category A: approved/standard alterations that predict sensitivity or resistance to approved/standard therapies

Category B: alterations that are inclusion or exclusion criteria for specific experimental therapies

Category C: alterations with limited evidence that predict sensitivity or resistance to standard or experimental therapies

Category D: alterations with prognostic or diagnostic utility

Category E: alterations with clear biologic significance in cancer (i.e., driver mutations) without clear clinical implications to date

Abbreviation: IGF-IR, insulin-like growth factor-I receptor.