TABLE 1.
Metabolic dependencies of therapy resistant cancer cells. Studies in this paper that have identified metabolic alterations in therapy resistant cancers are listed. Group numbers indicate the mechanism of metabolic rewiring.
| Group ID | Group dependency | References | First author | Cancer | Resistant to | Therapy to overcome metabolic resistance | Metabolic dependence mechanism | Evidence of oxphos alterations | Evidence for permanent or plastic oxphos adaptation |
|---|---|---|---|---|---|---|---|---|---|
| 1 | ETC | Lee et al. (2018) | Lee et al. | NSCLC | Irinotecan | Phenformin | Complex I of the ETC | Yes | Permanent |
| 1 | ETC | Ippolito et al. (2016) | Ippolito et al. | Prostate | Docetaxel | Metformin | Complex I of the ETC | Yes | Permanent |
| 1 | ETC | Farge et al. (2017) | Farge et al. | AML | Cytarabine | Metformin | Complex I of the ETC | Yes | Permanent |
| 1 | ETC | Wu et al. (2018) | Wu et al. | HCC | Doxorubicin | Rotenone | Complex I of the ETC | Yes | Permanent |
| 1 | ETC | McGuirk et al. (2021) | McGuirk et al. | Breast | Epirubicin | Biguanide phenformin | Complex I of the ETC | Yes | Permanent |
| 1 | ETC | Echeverria et al. (2019) | Echeverria et al. | TNBC, AML | Adriamycin Cyclophosphamide | IACS-010759 | Complex I of the ETC | Yes | Plastic |
| 1 | ETC | Xu et al. (2022) | Xu et al. | Bladder | Cisplatin | Phenformin | Complex I of the ETC | Yes | Plastic |
| 1 | ETC | Krysztofiak et al. (2021) | Krysztofiak et al. | Lung, Liver, Colorectal, Prostate, Brain, Breast | Ionizing Radiation | Rotenone | Complex I of the ETC | Yes | Plastic |
| 1 | ETC | Wu et al. (2018) | Wu et al. | HCC | Doxorubicin | Oligomycin | Complex V of the ETC | Yes | Permanent |
| 2 | FAS | Vazquez-Martin et al. (2007a) | Vazquez-Martin et al. | Breast | Trastuzumab | C75 | FASN | Untested | N/A |
| 2 | FAS | Menendez et al. (2004b) | Menendez et al. | Breast | Docetaxel | Cerulean | FASN | Untested | N/A |
| 2 | FAS | Menendez et al. (2005b) | Menendez et al. | Breast | Paclitaxel | C75 | FASN | Untested | N/A |
| 2 | FAS | Liu et al. (2008) | Liu et al. | Breast | Adriamycin | Orlistat | FASN | Untested | N/A |
| 2 | FAS | Vazquez-Martin et al. (2007b) | Vazquez-Martin et al. | Breast | 5-FU | Cerulenin | FASN | Untested | N/A |
| 2 | FAS | Menendez et al. (2004c) | Menendez et al. | Breast | Vinorelbine | Cerulenin | FASN | Untested | N/A |
| 3 | FAO | Tan et al. (2022) | Tan et al. | Ovarian | Cisplatin | Etomoxir | CPT1 | Yes | Permanent |
| 3 | FAO | Huang et al. (2021) | Huang et al. | Ovarian | Carboplatin | Etomoxir or Perhexiline | CPT1 | Yes | Permanent |
| 3 | FAO | Salunkhe et al. (2020) | Salunkhe et al. | Leukemia | Mitoxantrone | Etomoxir | CPT1 | Yes | Permanent |
| 3 | FAO | Li et al. (2022) | Li et al. | Breast | Paclitaxel | Knockdown of STAT3 and ACSL4 | CPT1 | Yes | Permanent |
| 3 | FAO | Wang et al. (2018) | Wang et al. | Breast | Paclitaxel | Perhexiline | CPT1 | Yes | Permanent |
| 3 | FAO | Stevens et al. (2020) | Stevens et al. | AML | Venetoclax and Azacytidine | Etomoxir | CPT1 | Yes | Permanent |
| 3 | FAO | Farge et al. (2017) | Farge et al. | AML | Cytarabine | Etomoxir | CPT1 | Yes | Permanent |
| 4 | LDs | Cotte et al. (2018) | Cotte et al. | Colorectal | Oxaliplatin and 5-FU | TSI-01 | LPCAT2 | Untested | N/A |
| 4 | LDs | Huang et al. (2019) | Huang et al. | NSCLC | Gefitinib | g-PPT | SCD1 | Untested | N/A |
| 4 | LDs | Sirois et al. (2019) | Sirois et al. | Breast | Doxorubicin or Paclitaxel | GW9662 | PPARG/PLIN4 | Yes | Permanent |
| 4 | LDs | Chen et al. (2020) | Chen et al. | Ovarian | Cisplatin | LLC | ABCs | Untested | N/A |
| 5 | Glycolysis | Shi et al. (2019) | Shi et al. | Colorectal | Oxaliplatin and 5-FU | 2-DG | HK2 | Untested | N/A |
| 5 | Glycolysis | He and Liu (2020) | He et al. | NSCLC | Cisplatin | 3-Bromopyruvate Acid | HK2 | Untested | N/A |
| 5 | Glycolysis | Qian et al. (2017) | Qian et al. | Gastric | Cisplatin | 2-DG | ENO1 | Untested | N/A |
| 5 | Glycolysis | Deng et al. (2021) | Deng et al. | Colorectal | 5-FU | miR-488 | PFKFB3 | Untested | N/a |
| 5 | Glycolysis | He et al. (2014) | He et al. | Colorectal | 5-FU | miR-122 | PKM2 | Untested | N/A |
| 5 | Glycolysis | Pan et al. (2016) | Pan et al. | Liver | Doxorubicin | miR-122 | PKM2 | Untested | N/A |
| 5 | Glycolysis | Zhou et al. (2010) | Zhou et al. | Breast | Paclitaxel | Oxamate | LDH | Untested | N/A |
| 5 | Glycolysis | Xu et al. (2018) | Xu et al. | Ovarian | Cisplatin | ABT737, 2-DG | Bcl-2, G6PD | Yes | Permanent |
| 5 | Glycolysis | Catanzaro et al. (2015) | Catanzaro et al. | Ovarian | Cisplatin | 6-aminonicotinamide | G6PDH | Yes | Permanent |
| 5 | Glycolysis | Zub et al. (2015) | Zub et al. | MM | Melphalan alkylating chemotherapy | dichloroacetate (DCA) | Glycolysis | Untested | N/A |
| 5 | Glycolysis | Zhou et al. (2015) | Zhou et al. | Lung | Paclitaxel | dichloroacetate (DCA) | Glycolysis | Untested | N/A |
| 6 | Glucose Oxidation | Marx et al. (2022) | Marx et al. | Colorectal | Irinotecan | Glucose deprivation | not tested | Yes | Permanent |
| 6 | Glucose Oxidation | Baek et al. (2023) | Baek et al. | Breast | Doxorubicin or Carboplatin | not tested | not tested | Yes | Plastic |
| 6 | Glucose Oxidation | Cai et al. (2020) | Cai et al. | Liver | Cisplatin | Metformin | GLUT1 | Untested | N/A |
| 7 | Glutamine Metabolism | McGuirk et al. (2021) | McGuirk et al. | Breast | Doxorubicin | Buthionine sulfoximine | Glutamate-cysteine ligase | Yes | Permanent |
| 7 | Glutamine Metabolism | Thompson et al. (2017) | Thompson | MM | Carfilzomib | CB-839 | Glutaminase (GLS) | Yes | Permanent |
| 7 | Glutamine Metabolism | Catanzaro et al. (2015) | Catanzaro et al. | Ovarian | Cisplatin | Glutamine free media | GLUT1 | Yes | Permanent |
| 7 | Glutamine Metabolism | Hernandez-Davies et al. (2015) | Hernandez-Davies et al. | Melanoma | Vemurafenib | BPTES and L-DON | Glutaminase (GLS) | Untested | N/a |
| 7 | Glutamine Metabolism | Catanzaro et al. (2015) | Catanzaro et al. | Ovarian and Cervical | Cisplatin | 2-DG | GLUT1 | Yes | Permanent |
| 7 | Glutamine Metabolism | Hudson et al. (2016) | Hudson et al. | Ovarian | Cisplatin | BPTES | Glutaminase (GLS) | Yes | Permanent |
| 7 | Glutamine Metabolism | Baenke et al. (2016) | Baenke et al. | Melanoma | PLX4720 | BPTES | Glutaminase (GLS) | Yes | Permanent |
| 7 | Glutamine Metabolism | van Gastel et al. (2020) | van Gastel et al. | AML | Cytarabine and Doxorubicin | L-DON | Glutamine metabolism | Untested | N/A |
| 8 | ROS | Song et al. (2020) | Song et al. | Breast | Gefitinib | Knockdown of GPX4 | GPX4 | Untested | N/A |
| 8 | ROS | Corazao-Rozas et al. (2013) | Corazao-Rozas et al. | Melanoma | PLX420 | Elesclomol | PGC1α | Yes | Permanent |
| 8 | ROS | Lee et al. (2018) | Lee et al. | NSCLC | Irinotecan | Gossypol | ALDH | Yes | Permanent |
| 8 | ROS | Lee et al. (2020) | Lee et al. | Colon, melanoma, prostate, ovary, stomach, pancreatic | Irinotecan or Vemurafenib or Cisplatin or Doxorubicin | Gossypol | ALDH | Yes | Permanent |
| 8 | ROS | Xu et al. (2018) | Xu et al. | Ovarian | Cisplatin | ABT737, 2-DG | Bcl-2, G6PD | Yes | Permanent |
| 9 | Other | Pandit et al. (2021) | Pandit et al. | HCC | Sorafenib | OPB-111077 | STAT | Yes | Permanent |
| 9 | Other | Bosc et al. (2021) | Bosc et al. | AML | Cytarabine | Venetoclax | BCL-2 | Yes | Permanent |
| 9 | Other | Farge et al. (2017) | Farge et al. | AML | Cytarabine | Tigecycline | Mitochondrial protein translation | Yes | Permanent |
| 9 | Other | Aroua et al. (2020) | Aroua et al. | AML | Cytarabine | Polyoxometalate 1 | ENTPD1 | Yes | Permanent |
| 9 | Other | van Gastel et al. (2020) | van Gastel et al. | AML | Cytarabine and Doxorubicin | Brequinar | Pyrimidine Synthesis | Untested | N/A |