Editing Metabolic pathway (section)

===Targeting the tricarboxylic acid cycle and glutaminolysis===
The [[tricarboxylic acid cycle]] (TCA) and [[glutaminolysis]] can also be targeted for cancer treatment, since they are essential for the survival and proliferation of cancer cells. [[Ivosidenib]] and [[enasidenib]], two FDA-approved cancer treatments, can arrest the TCA cycle of cancer cells by inhibiting isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2), respectively.<ref name="Frattaruolo"/>  Ivosidenib is specific to acute myeloid leukemia (AML) and cholangiocarcinoma, whereas enasidenib is specific to just acute myeloid leukemia (AML).

In a clinical trial consisting of 185 adult patients with cholangiocarcinoma and an IDH-1 mutation, there was a statistically significant improvement (p<0.0001; HR: 0.37) in patients randomized to ivosidenib. Still, some of the adverse side effects in these patients included fatigue, nausea, diarrhea, decreased appetite, ascites, and anemia.<ref>{{cite web |title=FDA approves Ivosidenib for advanced or metastatic cholangiocarcinoma |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-advanced-or-metastatic-cholangiocarcinoma |website=U.S. Food & Drug Administration|date=26 August 2021 }}</ref> In a clinical trial consisting of 199 adult patients with AML and an IDH2 mutation, 23% of patients experienced complete response (CR) or complete response with partial hematologic recovery (CRh) lasting a median of 8.2 months while on enasidenib. Of the 157 patients who required transfusion at the beginning of the trial, 34% no longer required transfusions during the 56-day time period on enasidenib. Of the 42% of patients who did not require transfusions at the beginning of the trial, 76% still did not require a transfusion by the end of the trial.  Side effects of enasidenib included nausea, diarrhea, elevated bilirubin and, most notably, differentiation syndrome.<ref>{{cite web |title=FDA granted regular approval to enasidenib for the treatment of relapsed or refractory AML |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-granted-regular-approval-enasidenib-treatment-relapsed-or-refractory-aml |website=U.S. Food & Drug Administration|date=9 February 2019 }}</ref>

[[Glutaminase]] (GLS), the enzyme responsible for converting glutamine to glutamate via hydrolytic deamidation during the first reaction of glutaminolysis, can also be targeted. In recent years, many small molecules, such as azaserine, acivicin, and CB-839 have been shown to inhibit glutaminase, thus reducing cancer cell viability and inducing apoptosis in cancer cells.<ref>{{cite journal | vauthors = Matés JM, Di Paola FJ, Campos-Sandoval JA, Mazurek S, Márquez J | title = Therapeutic targeting of glutaminolysis as an essential strategy to combat cancer | journal = Seminars in Cell & Developmental Biology | volume = 98 | pages = 34–43 | date = February 2020 | pmid = 31100352 | doi = 10.1016/j.semcdb.2019.05.012 | s2cid = 157067127 | doi-access = free | hdl = 10630/32822 | hdl-access = free }}</ref> Due to its effective antitumor ability in several cancer types such as ovarian, breast and lung cancers, CB-839 is the only GLS inhibitor currently undergoing clinical studies for FDA-approval.