TABLE 2.

List of pharmacogenes associated with cancer therapy and the evidence connecting them with extracellular vesicles (EVs).

Gene	Drug	Therapy type	Connection with extracellular vesicles: Examples	References a
Genes with pharmacogenetic drug prescribing recommendations b
CYP2D6	Tamoxifen	Hormone therapy	Protein detected in urine EVs (healthy donors, patients with nephropathy)	Moon et al. (2011)
DPYD	Capecitabine, fluorouracil, tegafur	Chemotherapy	Protein detected in glioblastoma cells EVs and in urine EVs (healthy donors)	Fraser et al. (2013), Pavlyukov et al. (2018)
TPMT	Mercaptopurine, thioguanine	Chemotherapy	Protein detected in various cancer cell line EVs and in urine EVs (healthy donors)	Hong et al. (2009), Wang et al. (2012), Bijnsdorp et al. (2013), Liang et al. (2013), Sinha et al. (2014), Liu et al. (2015), Hurwitz et al. (2016), Liem et al. (2017)
			mRNA detected in colorectal cancer cell EVs
UGT1A1	Irinotecan	Chemotherapy	Protein detected in platelet EVs	Dean et al. (2009), Liu et al. (2020)
			mRNA detected in plasma derived EVs in lung adenocarcinoma
Genes with PharmGKB level 2A clinical annotations
ABCB1	Methotrexate	Chemotherapy	Protein detected in various cancer cell line EVs, platelet EVs, serum EVs in prostate cancer and urine EVs (healthy donors)	Dean et al. (2009), Gonzales et al. (2009), Hong et al. (2009), Kato et al. (2015), Kharaziha et al. (2015), Hurwitz et al. (2016), Wang et al. (2019)
			mRNA detected in colorectal cancer cell EVs
NQ O 1	Alkylating agents, anthracyclines and related substances, fluorouracil, platinum compounds	Chemotherapy	Protein detected in various cancer cell line EVs and in urine EVs (healthy donors)	Hong et al. (2009), Welton et al. (2010), Wang et al. (2012), Ji et al. (2013), Hurwitz et al. (2016), Liem et al. (2017), Choi et al. (2018)
			mRNA detected in colorectal cancer cell EVs
MTHFR	Carboplatin, cisplatin, methotrexate	Chemotherapy	Protein detected in various cancer cell line EVs	Hong et al. (2009), Hurwitz et al. (2016), Liem et al. (2017)
			mRNA detected in colorectal cancer cell EVs
GSTP1	Fluorouracil, oxaliplatin, cyclophosphamide, epirubicin, platinum compounds	Chemotherapy	Protein detected in various cancer cell line EVs and in urine EVs (healthy donors, prostate cancer)	Skog et al. (2008), Gonzales et al. (2009), Hong et al. (2009), Welton et al. (2010), Fraser et al. (2013), Ji et al. (2013), Paggetti et al. (2015), Øverbye et al. (2015), Hurwitz et al. (2016), Yang S. et al. (2017), Lázaro-Ibáñez et al. (2017), Liem et al. (2017), Choi et al. (2018), Zhang et al. (2019)
			mRNA detected in colorectal cancer and glioblastoma cell EVs and serum derived EVs in breast cancer patients
SLCO1B1	Methotrexate	Chemotherapy	Not reported	—
TYMS	Capecitabine, fluorouracil	Chemotherapy	Protein detected in various cancer cell line EVs	Skog et al. (2008), Hong et al. (2009), Paggetti et al. (2015), Hurwitz et al. (2016), Liem et al. (2017), Choi et al. (2018)
			mRNA detected in colorectal cancer and glioblastoma cell EVs

^aReferences from individual functional/biomarker EV studies and EV-omics studies from VesiclePedia or Exocarta.

^bPharmacogenetic recommendations from CPIC or DPWG reported in PharmGKB, level 1A and 1B clinical annotations.