TABLE 1.
Gene-drug relationships.
| Gene | Drug | Relationship | Articles | Study method | Germline Vs Tumor Derived | Score |
|---|---|---|---|---|---|---|
| APC | EGFR-inhibitors | Sensitivity | Yang et al. (2019) | In vitro cell lines | Tumor derived | 2/4 |
| TNKS-inhibitors | Sensitivity | Schatoff et al. (2019) | In vivo models and human cell lines | Tumor derived | 2/4 | |
| Tanakaa et al. (2017) | Genomic scoring of clinical trial patient data, in vitro cell lines | Tumor derived | ||||
| Aspirin and NSAIDs | Shared risk outcome | FDA, (2018) | FDA label; Two randomized clinical trials | Germline | 4/4 | |
| Sensitivity | Burn et al. (2011) | Randomized controlled trial | Germline | 4/4 | ||
| Ishikawa et al. (2021) | Randomized controlled trial | Germline | ||||
| Samadder et al. (2018) | Secondary analysis of a randomized clinical trial | Germline | ||||
| BRCA1/2 | Oral Contraceptives | Clinical context consideration | Whittemore et al. (2004) | Retrospective study | Germline | 4/4 |
| Narod et al. (1998, 2001a) | Case-control questionnaire | Germline | ||||
| McGuire et al. (2004) | Case-control study | Germline | ||||
| Iodice et al. (2010) | Meta-analysis | Germline | ||||
| Huber et al. (2020) | Review | Germline | ||||
| Clomiphene Citrate | Shared risk outcome | FDA, (2012) | FDA label | Not specific | 1/4 | |
| Reigstad et al. (2017) | Population study | Not specific | ||||
| Estrogen-based replacement therapy | Clinical context consideration | Kotsopoulos et al. (2016) | Observational study | Germline | 3/4 | |
| Eisen et al. (2008) | Case-control study | Germline | ||||
| Domchek et al. (2011) | Case-control study | Germline | ||||
| Gordhandas et al. (2019) | Review | Germline | ||||
| Platinum compounds and Triple negative breast cancer | Sensitivity | Tutt et al. (2018) | Phase 3 Clinical Trial | Germline | 4/4 | |
| Caramelo et al. (2019) | Meta-analysis | Germline | ||||
| Silver et al. (2010) | Phase 2 Clinical Trial (BRCA1-specific) | Germline | ||||
| Byrski et al. (2014) | Phase 2 Clinical Trial (BRCA1-specific) | Germline | ||||
| Hahnen et al. (2017) | Secondary analysis of clinical trial | Germline | ||||
| PARP-inhibitors | Sensitivity | Farmer et al. (2005) | In vitro cell lines | Germline | 4/4 | |
| Madariaga et al. (2020) | Review | Germline | ||||
| Robson et al. (2017) | Phase 3 Clinical Trial | Germline | ||||
| Litton et al. (2018) | Phase 3 Clinical Trial | Germline | ||||
| Golan et al. (2019) | Phase 3 Clinical Trial | Germline | ||||
| Reiss et al. (2021) | Phase 2 Clinical Trial | Germline | ||||
| STK11 | PD-1 axis inhibitors | Resistance | Skoulidis et al. (2015) | Genomic analysis of tumor biopsies | Tumor derived | 2/4 |
| Skoulidis et al. (2018) | Retrospective cohort study | Tumor derived | ||||
| Schoenfeld et al. (2020) | Genomic analysis of tumor biopsies | Tumor derived | ||||
| Laderian et al. | Case series | Tumor derived | ||||
| ERK-inhibitors | Sensitivity | Caiola et al. (2020) | In vitro and in vivo | Tumor derived | 2/4 | |
| TSC1/2 | Estrogen based medications, including oral contraceptives | Shared risk outcome | Yano, (2002) | Case Report | Germline | 1/4 |
| Oberstein et al. (2003) | Case series - questionnaire | Germline | ||||
| Yu et al. (2009) | In vitro and vivo | Germline | ||||
| Yu et al. (2004) | In vitro cell lines | Germline | ||||
| TP53 | Genotoxic chemotherapy agents | Resistance | Frebourg et al. (2020) | Review | Germline | 2/4 |
| Kasper et al. (2018) | In vivo models | Germline | ||||
| Chemotherapy and Chronic Lymphocytic Leukemia | Resistance | Döhner et al. (1995) | Phase 3 Clinical Trial | Not specific | 4/4 | |
| Hallek et al. (2010) | Phase 3 Clinical Trial | Not specific | ||||
| Hallek (2019) | Review | Not specific | ||||
| Chemotherapy and Mantle Cell Lymphoma | Resistance | Eskelund et al. (2017) | Genomic analysis of tumor biopsies | Tumor derived | 2/4 | |
| Carboplatin and Breast Cancer | Sensitivity | Sheng et al. (2020) | Cohort Study | Germline | 3/4 | |
| 5-FU and Colon Cancer | Resistance | Aghabozorgi et al. (2020) | Review | Not specific | 3/4 | |
| PTEN | Tamoxifen | Shared risk outcome | Hobert and Eng, (2009) | Review | Yes | 1/4 |
| Trastuzumab and Lapatinib | Resistance | Berns et al. (2007) | In vitro cell lines | Tumor derived | 2/4 | |
| Nagata et al. (2004) | In vitro and vivo | Tumor derived | ||||
| Wang et al. (2011) | Expanded access clinical trial | Tumor derived | ||||
| Eichhorn et al. (2008) | In vitro and in vivo | Tumor derived | ||||
| CDK4/6 inhibitors | Resistance | Costa et al. (2020) | In vitro and in vivo | Tumor derived | 2/4 | |
| PI3K-alpha inhibitors | Resistance | Juric et al. (2015) | Case report | Tumor derived | 2/4 | |
| Costa et al. (2020) | In vitro and in vivo | Tumor derived | ||||
| VHL | HIF-2a inhibitors | Sensitivity | Chen et al. (2016) | Patient-derived tumorgraft | Tumor derived | 4/4 |
| Courtney et al. (2020) | Phase 1 Clinical Trial | Germline | ||||
| Choueiri et al. | Phase 1 Clinical Trial | Germline | ||||
| Jonasch et al. (2021) | Phase 2 Clinical Trial | Germline | ||||
| MUTYH | Alkylating agents | Resistance | Fry et al. (2008) | In vitro cell lines | Tumor derived | 2/4 |
| RET | GLP-1 agonists | Shared risk outcome | Bjerre Knudsen et al. (2010) | In vitro and in vivo | Tumor derived | 2/4 |
| Madsen et al. (2012) | In vitro and in vivo | Tumor derived | ||||
| FDA, (2010) | FDA label | Not specific | ||||
| Tyrosine Kinase Inhibitors | Sensitivity | O'Kane et al. (2019) | Phase 2 clinical trial | Germline | 4/4 | |
| Wells et al. (2012) | Phase 3 clinical trial | Germline | ||||
| Elisei et al. (2013) | Phase 3 clinical trial | Germline | ||||
| Wirth et al. (2020) | Phase 1/2 clinical trial | Germline | ||||
| Subbian et al. (2018) | In vitro and in vivo, two case reports | Tumor derived | ||||
| Subbian et al. (2021) | Phase 1/2 clinical trial | Germline | ||||
| SMAD4 | 5-FU | Resistance | Wasserman et al. (2019) | Cohort study | Tumor derived | 2/4 |
| Alhopuro et al. (2005) | In vitro cell lines | Tumor derived | ||||
| Papageorgis et al. (2011) | In vitro cell lines | Tumor derived | ||||
| Wong et al. (2020) | In vitro and in vivo | Tumor derived | ||||
| Cetuximab | Resistance | Lin et al. (2019) | In vitro cell lines | Tumor derived | 2/4 | |
| Ozawa et al. (2017) | In vitro and in vivo | Tumor derived | ||||
| Mei et al. | In vivo models | Tumor derived | ||||
| Irinotecan | Resistance | Wong et al. (2020) | In vitro and in vivo | Tumor derived | 2/4 | |
| Fluoroquinolones | Shared risk outcome | FDA warning | Cites 4 published observational studies | Not specific | 1/4 | |
| CIPRO | FDA label | Not specific | ||||
| SDHB | Temozolomide | Sensitivity | Hadoux et al. (2014) | Retrospective population study | Germline | 2/4 |
| Pang et al. (2018) | In vitro and in vivo, patient samples | Tumor derived | ||||
| Tyrosine Kinase Inhibitors | Resistance (GISTs) | Boikos et al. (2016) | Observational study | Germline | 2/4 | |
| Paik et al. (2014) | Case Report | Germline | ||||
| Sensitivity (Metastatic PGG and PCC) | O'Kane et al. (2019) | Phase 2 clinical trial | Germline | 3/4 | ||
| SDHA | Tyrosine Kinase Inhibitors | Resistance (GISTs) | Boikos et al. (2016) | Observational study | Germline | 2/4 |
| Sensitivity (Metastatic PGG and PCC) | O'Kane et al. (2019) | Phase 2 clinical trial | Germline | 3/4 | ||
| SDHC | Tyrosine Kinase Inhibitors | Sensitivity (RCC) | Shuch et al. (2016) | Case Report | Germline | 2/4 |
| MLH1 | Topoisomerase II inhibitors | Resistance | Fedier et al. (2001) | In vitro cell lines | Tumor derived | 2/4 |
| Aebi et al. (1997) | In vitro cell lines | Tumor derived | ||||
| Topoisomerase I inhibitors | Resistance | Fedier et al. (2001) | In vitro cell lines | Tumor derived | 2/4 | |
| Platinum agents | Resistance (Cisplatin and Carboplatin) | Aebi et al. (1997) | In vitro cell lines | Tumor derived | 2/4 | |
| Martin et al. (2008) | Review | Not specific | ||||
| Fink et al. (1997a) | In vitro and in vivo | Tumor derived | ||||
| Li et al. (2018) | In vitro and in vivo | Tumor derived | ||||
| Sensitivity (Oxaliplatin) | Fink et al. (1997a) | In vitro and in vivo | Tumor derived | 2/4 | ||
| Vaisman et al. (1998) | In vitro cell lines | Tumor derived | ||||
| 5-Fluorouracil | Resistance | Carethers et al. (1999) | In vitro cell lines | Tumor derived | 2/4 | |
| Meyers et al. (2001) | In vitro cell lines | Tumor derived | ||||
| Sargent et al. (2010) | Pooled analysis | Not specific | ||||
| Alkylating agents | Resistance | Taverna et al. (2000) | In vitro, human cell lines | Tumor derived | 2/4 | |
| Aspirin and NSAIDs | Sensitivity | Burn et al. (2020) | 10-years follow-up of randomized controlled trial | Germline | 4/4 | |
| Ouakrim et al. (2015) | Observational study | Germline | ||||
| Reyes-Uribe et al. (2021) | Phase 1 clinical trial | Germline | ||||
| MSH2 | Topoisomerase II inhibitors | Resistance | Fedier et al. (2001) | In vitro cell lines | Tumor derived | 2/4 |
| Aebi et al. (1997) | In vitro cell lines | Tumor derived | ||||
| Platinum agents | Resistance (Cisplatin and Carboplatin) | Aebi et al. (1997) | In vitro cell lines | Tumor derived | 2/4 | |
| Martin et al. (2008) | Review | Not specific | ||||
| Fink et al. (1997a) | In vitro and in vivo | Tumor derived | ||||
| Goodspeed et al. (2019) | CRISPR screen in cell line | Tumor derived | ||||
| Sensitivity (Oxaliplatin) | Fink et al. (1997a) | In vitro and in vivo | Tumor derived | 2/4 | ||
| 5-Fluorouracil | Resistance | Carethers et al. (1999) | In vitro cell lines | Tumor derived | 2/4 | |
| Sargent et al. (2010) | Pooled analysis | Tumor derived | ||||
| Alkylating agents | Resistance | Taverna et al. (2000) | In vitro, human cell lines | Tumor derived | 2/4 | |
| Friedman et al. (1997) | In vivo models | Tumor derived | ||||
| Aspirin and NSAIDs | Sensitivity | Burn et al. (2020) | 10-years follow-up of randomized controlled trial | Germline | 4/4 | |
| Ouakrim et al. (2015) | Observational study | Germline | ||||
| Reyes-Uribe et al. (2021) | Phase 1 clinical trial | Germline | ||||
| Mcilhatton et al. | In vivo model | Tumor derived | ||||
| MSH6 | Platinum agents | Resistance (Cisplatin) | Vaisman et al. (1998) | In vitro cell lines | Tumor derived | 2/4 |
| Sensitivity (Oxaliplatin) | Vaisman et al. (1998) | In vitro cell lines | Tumor derived | |||
| Temozolomide | Resistance | Nguyen et al. (2014) | In vitro and in vivo | Tumor derived | 2/4 | |
| Aspirin and NSAIDs | Sensitivity | Burn et al. (2020) | 10-years follow-up of randomized controlled trial | Germline | 4/4 | |
| Ouakrim et al. (2015) | Observational study | Germline | ||||
| Reyes-Uribe et al. (2021) | Phase 1 clinical trial | Germline | ||||
| PMS2 | Platinum agents | Resistance (Cisplatin) | Fink et al. (1997b) | In vitro cell lines | Tumor derived | 2/4 |
| Aspirin and NSAIDs | Sensitivity | Burn et al. (2020) | 10-year follow-up of randomized controlled trial | Germline | 4/4 | |
| Ouakrim et al. (2015) | Observational study | Germline | ||||
| Reyes-Uribe et al. (2021) | Phase 1 clinical trial | Germline |
Summary of gene-drug relationships, with description of references and evidence scoring.