Targeting Metabolism for Cancer Therapy

In the paper

“New insights into the differential metabolic dependencies of tumors have provided novel therapeutic strategies to exploit altered metabolism, some of which are being evaluated in pre-clinical models or clinical trials.”

In the paper

“Furthermore, the proliferation rates of normal cells are often greater than those of cancer cells (Vander Heiden and DeBerardinis, 2017), and prominent side effects of antimetabolite chemotherapy are caused by the destruction of normal rapidly proliferating cells.”

What the sources say

• Not checked yetcites Vander Heiden and DeBerardinis, 2017

In the paper

“Nevertheless, the fact that antimetabolite chemotherapies are clinically effective suggests that a metabolic therapeutic window exists beyond proliferation rate and response to DNA damage.”

In the paper

“The clinical success of antimetabolites for treating cancer is attributed to the increased metabolic demand of neoplastic cells for nucleotide biosynthesis and DNA replication.”

In the paper

“Indeed, activation of pyruvate kinase can inhibit cancer cell proliferation and tumor growth in some settings (Anastasiou et al., 2012; Kung et al., 2012; Walsh et al., 2010), but because pyruvate kinase expression is dispensable for the growth of some tumors (Cortes-Cros et al., 2013; Israelsen et al., 2013), whether pyruvate kinase activation will lead to durable responses remains an area of”

What the sources say

• Not checked yetcites Anastasiou et al., 2012 source
• Not checked yetcites Kung et al., 2012 source
• Not checked yetcites Walsh et al., 2010

In the paper

“In 1947, Sidney Farber, one of the pioneers of modern chemotherapy, discovered that aminopterin could cause disease remission in children with acute lymphoblastic leukemia (Dayton et al., 2016; Farber and Diamond, 1948).”

What the sources say

• Not checked yetcites Dayton et al., 2016 source
• Not checked yetcites Farber and Diamond, 1948

In the paper

“As a result, D-2HG accumulation in cancer cells expressing mutant IDH results in hypermethylation of histones and CpG islands in DNA (Figueroa et al., 2010; Lu et al., 2012; Turcan et al., 2012).”

What the sources say

• Not checked yetcites Figueroa et al., 2010 source
• Not checked yetcites Lu et al., 2012
• Not checked yetcites Turcan et al., 2012 source

In the paper

“Regardless of the underlying mechanism, alterations in basal enzymatic activity of a given reaction present potential vulnerabilities that might be targeted for cancer therapy.”

In the paper

“The expression of metabolic genes is frequently altered in cancer. Some changes in metabolic enzyme expression result from gene amplification or deletion, while others are downstream of growth signaling pathways or are the consequences of epigenetic changes. The activity of metabolic enzymes can also be affected by mutations in the genes encoding these enzymes.”

In the paper

“This phenomenon is now referred to as aerobic glycolysis, or the Warburg effect, and represents a striking metabolic difference between cancer and most normal tissues.”

In the paper

“Doses of 2-DG that inhibit glycolysis enough to limit cancer growth may not be tolerated due to similar effects in normal tissues that also rely on glucose metabolism.”

In the paper

“Targeting general proliferative metabolism may not offer an adequate therapeutic window since many non-malignant cells, including those in bone marrow, intestinal crypts, and hair follicles, are rapidly proliferating.”

In the paper

“Recurrent somatic point mutations in the genes coding for isocitrate dehydrogenase 1 and 2 (IDH1, IDH2) are found in a wide variety of cancers, including glioblastoma multiforme (GBM) (Yan et al., 2009) and acute myeloid leukemia (AML) (Dang et al., 2016; Mardis et al., 2009).”

What the sources say

• Not checked yetcites Yan et al., 2009 source
• Not checked yetcites Dang et al., 2016 source
• Not checked yetcites Mardis et al., 2009 source

In the paper

“Inducing DNA damage with the use of genotoxic chemotherapies can sensitize cells to inhibitors of nucleotide biosynthesis (Brown et al., 2017; Peters et al., 2000), suggesting that oncogenic mutations that reduce the DNA damage response is one explanation for why a therapeutic window exists for antimetabolite compounds.”

In the paper

“Inducing DNA damage with the use of genotoxic chemotherapies can sensitize cells to inhibitors of nucleotide biosynthesis (Brown et al., 2017; Peters et al., 2000), suggesting that oncogenic mutations that reduce the DNA damage response is one explanation for why a therapeutic window exists for antimetabolite compounds.”

What the sources say

• Not checked yetcites Brown et al., 2017 source
• Not checked yetcites Peters et al., 2000 source

In the paper

“Numerous preclinical studies have demonstrated anti-proliferative effects of 2-DG (Zhang et al., 2014a).”

What the sources say

• Not checked yetcites Zhang et al., 2014a

In the paper

“Despite challenges associated with targeting glucose metabolism directly, glucose uptake by cancer cells has been successfully exploited in patients through the use of the fluoro-deoxyglucose positron-emission-tomography (FDG-PET) imaging to stage cancers and assess response to therapy (d’Amico, 2015; Farwell et al., 2014; Zhu et al., 2011).”

What the sources say

• Not checked yetcites d’Amico, 2015
• Not checked yetcites Farwell et al., 2014 source
• Not checked yetcites Zhu et al., 2011 source

In the paper

“Paradoxically, decreased pyruvate kinase activity is associated with increased aerobic glycolysis, suggesting the activation of pyruvate kinase activity might be a way to target cancer (Christofk et al., 2008).”

What the sources say

• Not checked yetcites Christofk et al., 2008 source

In the paper

“The relative lack of 2-DG clinical efficacy at tolerable doses has been echoed by most other attempts to directly target aerobic glycolysis.”

In the paper

“but because pyruvate kinase expression is dispensable for the growth of some tumors (Cortes-Cros et al., 2013; Israelsen et al., 2013), whether pyruvate kinase activation will lead to durable responses remains an area of active study”

What the sources say

• Not checked yetcites Cortes-Cros et al., 2013 source
• Not checked yetcites Israelsen et al., 2013 source

In the paper

“Cancers expressing mutant IDH represent a unique case in which a metabolic enzyme can act as an oncogene and contribute to tumor development.”

In the paper

“Mammals have two glutaminase genes, GLS and GLS2, and targeting the enzymes encoded by these genes with chemical inhibitors has been found to decrease cancer cell proliferation in both in vitro and in vivo models (Gross et al., 2014; Jacque et al., 2015; Le et al., 2012; Xiang et al., 2015; Yuneva et al., 2012).”

What the sources say

• Not checked yetcites Gross et al., 2014 source
• Not checked yetcites Jacque et al., 2015 source
• Not checked yetcites Le et al., 2012

In the paper

“Emerging work suggests that increased serine synthesis may be particularly important for maintaining redox homeostasis during metastasis (Piskounova et al., 2015).”

What the sources say

• Not checked yetcites Piskounova et al., 2015 source

In the paper

“Serine is present in plasma and can be taken up by cells via amino acid transporters, yet PHGDH expression and increased serine biosynthesis have been shown to be important for supporting cancer cell proliferation and survival in both in vitro and in vivo settings (Locasale et al., 2011; Possemato et al., 2011).”

What the sources say

• Not checked yetcites Locasale et al., 2011 source
• Not checked yetcites Possemato et al., 2011 source

In the paper

“Glutamine metabolism is upregulated by various oncogenic signaling pathways (Altman et al., 2016).”

What the sources say

• Not checked yetcites Altman et al., 2016 source

In the paper

“There is also data that GLS2 activity can be tumor suppressive (Hu et al., 2010), underscoring the importance of defining the patient population likely to benefit from glutaminase inhibition.”

What the sources say

• Not checked yetcites Hu et al., 2010

In the paper

“Glutamine carbon has been found to contribute to aspartate, glutamate and tricarboxylic acid (TCA) cycle metabolites via glutaminolysis (Figure 5) (Altman et al., 2016).”

What the sources say

• Not checked yetcites Altman et al., 2016 source

In the paper

“Certain tumors are dependent on uptake of environmental serine (Jain et al., 2012; Maddocks et al., 2013; Maddocks et al., 2017), and limiting plasma serine availability can be beneficial for patients with these cancers.”

What the sources say

• Not checked yetcites Jain et al., 2012 source
• Not checked yetcites Maddocks et al., 2013 source
• Not checked yetcites Maddocks et al., 2017 source

In the paper

“Functional PHGDH loss is toxic to tumor cells with PHGDH amplification or high serine biosynthetic flux (Locasale et al., 2011; Mattaini et al., 2015; Possemato et al., 2011; Zhang et al., 2017), and small-molecule inhibitors targeting PHGDH have been shown to inhibit serine synthesis and tumor proliferation in vitro and in xenograft cancer models (Mullarky et al., 2016; Pacold et al., 2016; Wang”

What the sources say

• Not checked yetcites Locasale et al., 2011 source
• Not checked yetcites Mattaini et al., 2015 source
• Not checked yetcites Possemato et al., 2011 source

In the paper

“Importantly, inhibiting glutamine entry into the TCA cycle can blunt tumor progression in a MYC-driven cancer model of liver cancer (Xiang et al., 2015; Yuneva et al., 2012) and a MYC-inducible Burkitt lymphoma model (Le et al., 2012; Xiang et al., 2015).”

What the sources say

• Not checked yetcites Xiang et al., 2015 source
• Not checked yetcites Yuneva et al., 2012 source
• Not checked yetcites Le et al., 2012

In the paper

“With respect to proliferating cells such as cancer, serine is the primary carbon donor to the tetrahydrofolate (THF) cycle, which is required for both purine and pyrimidine nucleotide biosynthesis (Figure 6)(Snell et al., 1987).”

What the sources say

• Not checked yetcites Snell et al., 1987 source

In the paper

“and therapies that deplete exogenous arginine (Table 1) may be effective in treating malignancies where FH is lost (Phillips et al., 2013).”

What the sources say

• Not checked yetcites Phillips et al., 2013 source

In the paper

“Loss of metabolic enzyme expression can also occur as a passenger event. For example, genomic deletions leading to loss of tumor suppressor genes can also lead to loss of adjacent non-essential metabolic genes.”

In the paper

“Furthermore, ENO1 loss results in extreme sensitivity to the pan-enolase inhibitor phosphonoacetohydroxamate (PHAH) and SF2312 (Leonard et al., 2016; Muller et al., 2012).”

What the sources say

• Not checked yetcites Leonard et al., 2016 source
• Not checked yetcites Muller et al., 2012 source

In the paper

“Recombinant pegylated arginine deiminase (ADI-PEG20) has been tested in clinical trials to treat melanoma and hepatocellular carcinoma with some therapeutic benefit (Ascierto et al., 2005; Izzo et al., 2004; Ott et al., 2013; Szlosarek et al., 2013; Yang et al., 2010).”

What the sources say

• Not checked yetcites Ascierto et al., 2005 source
• Not checked yetcites Izzo et al., 2004 source
• Not checked yetcites Ott et al., 2013 source

In the paper

“To cope with TCA cycle truncation and still produce aspartate, SDH defective cells upregulate PC protein expression in culture and in tumors to synthesize aspartate from glucose (Cardaci et al., 2015; Lussey-Lepoutre et al., 2015).”

What the sources say

• Not checked yetcites Cardaci et al., 2015 source
• Not checked yetcites Lussey-Lepoutre et al., 2015 source

In the paper

“Combining serine restriction with other drugs may also potentiate antitumor responses (Gravel et al., 2014; Maddocks et al., 2013; Maddocks et al., 2017).”

What the sources say

• Not checked yetcites Gravel et al., 2014 source
• Not checked yetcites Maddocks et al., 2013 source
• Not checked yetcites Maddocks et al., 2017 source

In the paper

“MTAP loss results in reduced PRMT5 activity and renders MTAP-null cancer cell more sensitive to PRMT5 depletion than isogenic counterparts that express MTAP (Kryukov et al., 2016; Marjon et al., 2016; Mavrakis et al., 2016).”

What the sources say

• Not checked yetcites Kryukov et al., 2016 source
• Not checked yetcites Marjon et al., 2016 source
• Not checked yetcites Mavrakis et al., 2016 source

In the paper

“However, the use of arginine-catabolizing enzymes may not be an effective therapeutic strategy for all ASS1-deficient cancers, as some ADI-treated tumors have been found to re-express ASS1 (Feun et al., 2012; Long et al., 2013; Shen et al., 2003).”

What the sources say

• Not checked yetcites Feun et al., 2012 source
• Not checked yetcites Long et al., 2013 source
• Not checked yetcites Shen et al., 2003 source

In the paper

“Consequently, FH deletion renders mouse and human cells more sensitive to genetic and pharmacological inhibition of heme oxygenase 1 (Hmox1), an enzyme involved in heme degradation.”

What the sources say

• Not checked yetcites Frezza et al., 2011 source

In the paper

“Additionally, ablation of methionine adenosyltransferase II alpha (MAT2A), the enzyme that produces the canonical and high-affinity PRMT5 substrate, S-adenosylmethionine (SAM), also reduces PRMT5-dependent methylation and proliferation in MTAP-deleted cancer cells (Marjon et al., 2016).”

What the sources say

• Not checked yetcites Marjon et al., 2016 source

In the paper

“Genetic or epigenetic silencing of ASS1 expression provides an advantage to tumor cells by allowing them to preserve cellular aspartate (Rabinovich et al., 2015), a poorly transported nutrient that can be a critical output of the TCA cycle to support de novo nucleotide synthesis and cell proliferation (Birsoy et al., 2015; Sullivan et al., 2015).”

What the sources say

• Not checked yetcites Rabinovich et al., 2015 source
• Not checked yetcites Birsoy et al., 2015 source
• Not checked yetcites Sullivan et al., 2015 source

In the paper

“Co-administration of MTA with toxic adenosine analogues has been shown to be selectively lethal to MTAP deficient cancer cells, since MTAP-expressing normal tissues are able to convert MTA to adenine to competitively inhibit the effects of the analogues (Lubin and Lubin, 2009).”

What the sources say

• Not checked yetcites Lubin and Lubin, 2009

In the paper

“Like D-2HG, fumarate and succinate accumulation can inhibit some αKG-dependent dioxygenases, resulting in hypermethylation of DNA and histones in tumors exhibiting loss of FH or SDH (Hoekstra et al., 2015; Letouze et al., 2013; Xiao et al., 2012).”

What the sources say

• Not checked yetcites Hoekstra et al., 2015 source
• Not checked yetcites Letouze et al., 2013 source
• Not checked yetcites Xiao et al., 2012 source

In the paper

“Because cells often exhibit redundancy in essential pathways, this phenomenon can introduce a therapeutic opportunity to target cancer cells that has been termed collateral lethality (Muller et al., 2015).”

What the sources say

• Not checked yetcites Muller et al., 2015 source

In the paper

“For example, some melanoma, lymphoma, glioma, and prostate cancers reduce or lose the expression of the urea cycle enzyme argininosuccinate synthase 1 (ASS1) (Delage et al., 2010).”

What the sources say

• Not checked yetcites Delage et al., 2010 source

In the paper

“Familial cancer syndromes caused by fumarate hydratase (FH) or succinate dehydrogenase (SDH) deletion suggest that these TCA enzymes can behave as classical tumor suppressors.”

What the sources say

• Not checked yetcites Baysal et al., 2000 source
• Not checked yetcites Tomlinson et al., 2002 source

In the paper

“but was found to be clinically ineffective in patients with advanced MTAP-deficient tumors in a Phase II trial (Kindler et al., 2009).”

What the sources say

• Not checked yetcites Kindler et al., 2009 source

In the paper

“Deletion of the tumor suppressor CDKN2A results in concomitant deletion of the methionine salvage pathway enzyme methylthioadenosine phosphorylase (MTAP) in many cancers, including 53% of glioblastomas and 26% of pancreatic cancers (Mavrakis et al., 2016).”

What the sources say

• Not checked yetcites Mavrakis et al., 2016 source

In the paper

“Pharmacokinetic analyses confirming successful purine biosynthesis inhibition by doses of L-alanosine used in the study were not reported, so further exploration of why this approach failed may yield insight into how best to exploit MTAP deficiency.”

In the paper

“However, mitochondrial ATP production appears dispensable for many proliferating cells (Birsoy et al., 2015; Sullivan et al., 2015; Titov et al., 2016).”

What the sources say

• Not checked yetcites Birsoy et al., 2015 source
• Not checked yetcites Sullivan et al., 2015 source
• Not checked yetcites Titov et al., 2016 source

In the paper

“Several lines of evidence suggest that targeting de novo fatty acid synthesis might be effective in the treatment of some cancers.”

In the paper

“With the exception of liver, adipose tissue, and lactating breast, adult tissues do not synthesize fatty acids de novo under normal physiological conditions (Menendez and Lupu, 2006), so inhibition of de novo fatty acid synthesis might have an adequate therapeutic window.”

What the sources say

• Not checked yetcites Menendez and Lupu, 2006

In the paper

“Respiration is also needed for tumor initiation, as tumor cells with impaired oxidative phosphorylation due to depletion of mitochondrial DNA (mtDNA) exhibit increased tumor latency upon subcutaneous transplantation.”

What the sources say

• Not checked yetcites Tan et al., 2015a

In the paper

“Genetic knockdown of ACC induces apoptosis in cancer cell lines (Brusselmans et al., 2005; Chajes et al., 2006), and an allosteric inhibitor of ACC, ND-646, has shown antitumor efficacy in autochthonous mouse lung tumor models (Svensson et al., 2016).”

What the sources say

• Not checked yetcites Svensson et al., 2016 source

In the paper

“Small-molecules targeting NAMPT can be effective anti-tumor agents in vitro and in xenograft cancer models (Nahimana et al., 2009; Tan et al., 2015b; Watson et al., 2009).”

What the sources say

• Not checked yetcites Nahimana et al., 2009 source
• Not checked yetcites Tan et al., 2015b
• Not checked yetcites Watson et al., 2009 source

In the paper

“Instead, respiration serves an alternative anabolic role for proliferating cells by regenerating the oxidized form of nicotinamide adenine dinucleotide (NAD+) from the reduced form (NADH) (Birsoy et al., 2015; Sullivan et al., 2015; Titov et al., 2016).”

What the sources say

• Not checked yetcites Birsoy et al., 2015 source
• Not checked yetcites Sullivan et al., 2015 source
• Not checked yetcites Titov et al., 2016 source

In the paper

“ACLY activity is elevated in cancers (Migita et al., 2008), and targeting ACLY genetically or chemically prevents xenograft tumor formation and proliferation (Adam et al., 2013; Bauer et al., 2005; Hatzivassiliou et al., 2005; Migita et al., 2008).”

What the sources say

• Not checked yetcites Adam et al., 2013 source
• Not checked yetcites Bauer et al., 2005 source
• Not checked yetcites Hatzivassiliou et al., 2005 source

In the paper

“ACLY activity is elevated in cancers (Migita et al., 2008), and targeting ACLY genetically or chemically prevents xenograft tumor formation and proliferation (Adam et al., 2013; Bauer et al., 2005; Hatzivassiliou et al., 2005; Migita et al., 2008).”

What the sources say

• Not checked yetcites Migita et al., 2008 source

In the paper

“However, subsequent work determined that despite engaging in aerobic glycolysis, cancer cells consume oxygen at levels comparable to normal tissue (Weinhouse, 1956; Zu and Guppy, 2004).”

What the sources say

• Not checked yetcites Weinhouse, 1956 source
• Not checked yetcites Zu and Guppy, 2004

In the paper

“In clinical trials, use of these inhibitors as single agents has not caused tumor remission (von Heideman et al., 2010), but additional studies may uncover how best to safely use these drugs for patient benefit.”

What the sources say

• Not checked yetcites von Heideman et al., 2010 source

In the paper

“Although the precise mechanism of metformin action remains controversial (Luengo et al., 2014), recent work has shown that the anti-tumorigenic effect of metformin can at least be partially accounted for by direct mitochondrial complex I inhibition in tumors (Gui et al., 2016; Wheaton et al., 2014).”

What the sources say

• Not checked yetcites Gui et al., 2016 source
• Not checked yetcites Wheaton et al., 2014 source

In the paper

“Since then, numerous studies have identified de novo fatty acid biosynthesis as a key metabolic requirement for some cancers, and it has been dubbed by some as a distinct metabolic “hallmark of the transformed phenotype” (Kuhajda et al., 1994; Menendez and Lupu, 2006; Rohrig and Schulze, 2016).”

What the sources say

• Not checked yetcites Kuhajda et al., 1994 source
• Not checked yetcites Menendez and Lupu, 2006
• Not checked yetcites Rohrig and Schulze, 2016 source

In the paper

“With the exception of liver, adipose tissue, and lactating breast, adult tissues do not synthesize fatty acids de novo under normal physiological conditions (Menendez and Lupu, 2006), so inhibition of de novo fatty acid synthesis might have an adequate therapeutic window.”

What the sources say

• Not checked yetcites Menendez and Lupu, 2006

In the paper

“Cancer cells are also able to generate acetyl-CoA from cytosolic acetate (Comerford et al., 2014; Gao et al., 2016; Kamphorst et al., 2014; Mashimo et al., 2014).”

What the sources say

• Not checked yetcites Comerford et al., 2014 source
• Not checked yetcites Gao et al., 2016 source
• Not checked yetcites Kamphorst et al., 2014 source

In the paper

“However, PRMT5 inhibitors in current clinical trials may not be effective in MTAP null cancers, in part because the high levels of MTA in these cells compete for binding of the inhibitors to the enzyme.”

In the paper

“Genetic knockdown of ACC induces apoptosis in cancer cell lines (Brusselmans et al., 2005; Chajes et al., 2006), and an allosteric inhibitor of ACC, ND-646, has shown antitumor efficacy in autochthonous mouse lung tumor models (Svensson et al., 2016).”

What the sources say

• Not checked yetcites Brusselmans et al., 2005 source
• Not checked yetcites Chajes et al., 2006 source

In the paper

“Metformin has also been found to cooperate with neo-adjuvant chemotherapy to result in complete tumor regression in some breast cancer patients (Jiralerspong et al., 2009).”

What the sources say

• Not checked yetcites Jiralerspong et al., 2009 source

In the paper

“For example, eliminating environmental serine, limiting aspartate synthesis via mitochondrial inhibition, and ablating the mitochondrial folate pathway impairs purine biosynthesis (Ducker et al., 2016; Labuschagne et al., 2014; Sullivan et al., 2015).”

What the sources say

• Not checked yetcites Ducker et al., 2016 source
• Not checked yetcites Labuschagne et al., 2014 source
• Not checked yetcites Sullivan et al., 2015 source

In the paper

“Though nucleotide salvage pathways can support tumor cell proliferation in certain contexts (Tabata et al., 2017), concentrations of circulating nucleotides are likely too low for many tumors to satisfy their nucleotides demand via salvage alone (Traut, 1994).”

What the sources say

• Not checked yetcites Traut, 1994 source

In the paper

“KRAS/LKB1-null lung cancer cells are more reliant on the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1) for pyrimidine biosynthesis, although this dependency is independent of mTOR signaling (Kim et al., 2017).”

What the sources say

• Not checked yetcites Kim et al., 2017 source

In the paper

“Inhibitors of mutant IDH1 or IDH2 have been shown to induce differentiation in AML cells harboring mutant IDH (Okoye-Okafor et al., 2015; Wang et al., 2013).”

What the sources say

• Not checked yetcites Okoye-Okafor et al., 2015 source
• Not checked yetcites Wang et al., 2013 source

In the paper

“Together, these observations suggest that tissue-of-origin can influence metabolic requirements and vulnerabilities.”

In the paper

“Acute lymphoblastic leukemia (ALL) and related lymphomas, however, are auxotrophic for asparagine (Neuman and McCoy, 1956).”

What the sources say

• Not checked yetcites Neuman and McCoy, 1956

In the paper

“The absence of a genetic driver for asparagine auxotrophy, combined with the fact that L-asparaginase has little known clinical utility outside of the context of ALL, suggests that this metabolic vulnerability may be lineage dependent.”

In the paper

“Activation of mTOR can increase ribose synthesis via the oxidative pentose phosphate pathway (Duvel et al., 2010) and enhance flux through the pyrimidine and purine synthesis pathways (Ben-Sahra et al., 2013; Ben-Sahra et al., 2016; Robitaille et al., 2013), suggesting that targeting nucleotide metabolism in tumor contexts with mTOR hyperactivation may be more effective.”

What the sources say

• Not checked yetcites Duvel et al., 2010 source
• Not checked yetcites Ben-Sahra et al., 2013 source
• Not checked yetcites Ben-Sahra et al., 2016 source

In the paper

“Thus, administering 5hmdC and 5fdC may selectively target tumors overexpressing CDA.”

In the paper

“In fact, genome-wide analysis has shown that there is no consistent gene expression pattern that dictates sensitivity to L-asparaginase (Fine et al., 2005).”

What the sources say

• Not checked yetcites Fine et al., 2005 source

In the paper

“Recently, it has been determined that mouse lung and pancreatic tumors exhibit differences in amino acid metabolism, even when harboring the same genetic lesion.”

What the sources say

• Not checked yetcites Mayers et al., 2016 source

In the paper

“Recently, a myeloid cell screen involving HoxA9-enforced differentiation arrest found that inhibition of dihydroorotate dehydrogenase (DHODH), an enzyme in the pyrimidine biosynthesis pathway (Figure 1b), can induce differentiation (Sykes et al., 2016).”

What the sources say

• Not checked yetcites Sykes et al., 2016 source

In the paper

“In fact, tumors retain many features that correspond to their parental normal tissue (Gaude and Frezza, 2016; Hu et al., 2013).”

What the sources say

• Not checked yetcites Gaude and Frezza, 2016
• Not checked yetcites Hu et al., 2013

In the paper

“Though the mechanism of asparagine auxotrophy in ALL cells was assumed to be genetically defined, studies have shown that clinical response to L-asparaginase treatment is independent of asparagine synthase (ASNS) expression, the enzyme that converts aspartate to asparagine (Figure 7) (Appel et al., 2006; Stams et al., 2003).”

What the sources say

• Not checked yetcites Appel et al., 2006 source
• Not checked yetcites Stams et al., 2003 source

In the paper

“Though nucleotide salvage pathways can support tumor cell proliferation in certain contexts (Tabata et al., 2017), concentrations of circulating nucleotides are likely too low for many tumors to satisfy their nucleotides demand via salvage alone (Traut, 1994).”

What the sources say

• Not checked yetcites Tabata et al., 2017 source

In the paper

“Cancer cells generally have increased levels of reactive metabolites (DeBerardinis and Chandel, 2016; Sullivan et al., 2016).”

What the sources say

• Not checked yetcites DeBerardinis and Chandel, 2016
• Not checked yetcites Sullivan et al., 2016 source

In the paper

“Tumors of other lineages are also dependent on BCAA transaminases, including some glioblastomas and blast crisis chronic myeloid leukemia (Hattori et al., 2017; Tonjes et al., 2013).”

What the sources say

• Not checked yetcites Hattori et al., 2017 source
• Not checked yetcites Tonjes et al., 2013 source

In the paper

“Inhibitors of this transporter have been found to deplete intracellular glutathione in cancer cells, resulting in iron-dependent accumulation of ROS and a form of cell death termed ferroptosis (Dixon et al., 2012; Dixon et al., 2014; Yang et al., 2014).”

What the sources say

• Not checked yetcites Dixon et al., 2012 source
• Not checked yetcites Dixon et al., 2014 source
• Not checked yetcites Yang et al., 2014 source

In the paper

“Therapeutic interventions that decrease intracellular glutathione levels, such as administration of the oxidized form of vitamin C, dehydroascorbate (DHA), can result in cancer cell death and impaired tumor progression (Yun et al., 2015)”

What the sources say

• Not checked yetcites Yun et al., 2015 source

In the paper

“While elevation of reactive metabolites can support oncogenesis in some contexts (Arnold et al., 2001; Irani et al., 1997; Suh et al., 1999; Weinberg et al., 2010), at high levels reactive metabolites become toxic and kill cells due to the resulting damage to the proteome and genome (Karisch et al., 2011; Rabbani and Thornalley, 2014).”

What the sources say

• Not checked yetcites Arnold et al., 2001 source
• Not checked yetcites Irani et al., 1997 source
• Not checked yetcites Suh et al., 1999 source

In the paper

“PTEN-deficient cells, which have active mTOR signaling, are more sensitive to inhibition of DHODH by brequinar and leflunomide (Mathur et al., 2017).”

What the sources say

• Not checked yetcites Mathur et al., 2017 source

In the paper

“While elevation of reactive metabolites can support oncogenesis in some contexts (Arnold et al., 2001; Irani et al., 1997; Suh et al., 1999; Weinberg et al., 2010), at high levels reactive metabolites become toxic and kill cells due to the resulting damage to the proteome and genome (Karisch et al., 2011; Rabbani and Thornalley, 2014).”

What the sources say

• Not checked yetcites Karisch et al., 2011 source
• Not checked yetcites Rabbani and Thornalley, 2014 source

In the paper

“It has been reported that lactate produced by cancer-associated fibroblasts can enter the TCA cycle of cancer cells (Bonuccelli et al., 2014; Witkiewicz et al., 2012), and lactate produced in hypoxic regions of a tumor can fuel respiration in well-oxygenated tumor cells (Kennedy et al., 2013; Sonveaux et al., 2008).”

What the sources say

• Not checked yetcites Bonuccelli et al., 2014 source
• Not checked yetcites Witkiewicz et al., 2012 source

In the paper

“It has been reported that lactate produced by cancer-associated fibroblasts can enter the TCA cycle of cancer cells (Bonuccelli et al., 2014; Witkiewicz et al., 2012), and lactate produced in hypoxic regions of a tumor can fuel respiration in well-oxygenated tumor cells (Kennedy et al., 2013; Sonveaux et al., 2008).”

What the sources say

• Not checked yetcites Kennedy et al., 2013 source
• Not checked yetcites Sonveaux et al., 2008

In the paper

“Importantly, cell lines derived from resistant lung tumors become sensitive to glutaminase inhibition in vitro, highlighting that environment can be a contributor to glutaminase sensitivity (Davidson et al., 2016).”

What the sources say

• Not checked yetcites Davidson et al., 2016 source

In the paper

“There is growing evidence that metabolic dependencies in cancer are influenced by tissue environment, cancer lineage, as well as genetic events.”

In the paper

“Even among cancers where mutant IDH is an oncogenic driver, sensitivity to mutant IDH inhibitors appears to differ between leukemia and solid tumor models (Tateishi et al., 2015; Turcan et al., 2013).”

What the sources say

• Not checked yetcites Tateishi et al., 2015 source
• Not checked yetcites Turcan et al., 2013 source