Aberrant Lipid Metabolic Signatures in Acute Myeloid Leukemia.

Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30%-80% experiencing it within 2 years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant leukemic stem cells (LSCs). These cells express genes related to stemness that are frequently difficult to eradicate and tend to survive standard treatments. Studies have demonstrated that by targeting the metabolic pathways of LSCs, it is possible to improve outcomes and extend the survival of those afflicted by leukemia. The overwhelming evidence suggests that lipid metabolism is reprogrammed in LSCs, leading to an increase in fatty acid uptake and de novo lipogenesis. Genes regulating this process also play a crucial role in therapy evasion. In this concise review, we summarize the lipid metabolism in normal hematopoietic cells, AML blast cells, and AML LSCs. We also compare the lipid metabolic signatures in de novo versus therapy-resistant AML blast and LSCs. We further discuss the metabolic switches, cellular crosstalk, potential targets, and inhibitors of lipid metabolism that could alleviate treatment resistance and relapse.

Type 1 collagen: Synthesis, structure and key functions in bone mineralization.

Collagen is a highly abundant protein in the extracellular matrix of humans and mammals, and it plays a critical role in maintaining the body's structural integrity. Type I collagen is the most prevalent collagen type and is essential for the structural integrity of various tissues. It is present in nearly all connective tissues and is the main constituent of the interstitial matrix. Mutations that affect collagen fiber formation, structure, and function can result in various bone pathologies, underscoring the significance of collagen in sustaining healthy bone tissue. Studies on type 1 collagen have revealed that mutations in its encoding gene can lead to diverse bone diseases, such as osteogenesis imperfecta, a disorder characterized by fragile bones that are susceptible to fractures. Knowledge of collagen's molecular structure, synthesis, assembly, and breakdown is vital for comprehending embryonic and foetal development and several aspects of human physiology. In this review, we summarize the structure, molecular biology of type 1 collagen, its biomineralization and pathologies affecting bone.

Predominant factors influencing reactive oxygen species in cancer stem cells.

Reactive oxygen species (ROS) and its related signaling pathways and regulating molecules play a major role in the growth and development of cancer stem cells. The concept of ROS and cancer stem cells (CSCs) has been gaining much attention since the past decade and the evidence show that these CSCs possess robust self-renewal and tumorigenic potential and are resistant to conventional chemo- and radiotherapy and believed to be responsible for tumor progression, metastasis, and recurrence. It seems reasonable to say that cancer can be cured only if the CSCs are eradicated. ROS are Janus-faced molecules that can regulate cellular physiology as well as induce cytotoxicity, depending on the magnitude, duration, and site of generation. Unlike normal cancer cells, CSCs expel ROS efficiently by upregulating ROS scavengers. This unique redox regulation in CSCs protects them from ROS-mediated cell death and nullifies the effect of radiation, leading to chemoresistance and radioresistance. However, how these CSCs control ROS production by scavenging free radicals and how they maintain low levels of ROS is a challenging to understand and these attributes make CSCs as prime therapeutic targets. Here, we summarize the mechanisms of redox regulation in CSCs, with a focus on therapy resistance, its various pathways and microRNAs regulation, and the potential therapeutic implications of manipulating the ROS levels to eradicate CSCs. A better understanding of these molecules, their interactions in the CSCs may help us to adopt proper control and treatment measures.

Natural compounds targeting nuclear receptors for effective cancer therapy.

Human nuclear receptors (NRs) are a family of forty-eight transcription factors that modulate gene expression both spatially and temporally. Numerous biochemical, physiological, and pathological processes including cell survival, proliferation, differentiation, metabolism, immune modulation, development, reproduction, and aging are extensively orchestrated by different NRs. The involvement of dysregulated NRs and NR-mediated signaling pathways in driving cancer cell hallmarks has been thoroughly investigated. Targeting NRs has been one of the major focuses of drug development strategies for cancer interventions. Interestingly, rapid progress in molecular biology and drug screening reveals that the naturally occurring compounds are promising modern oncology drugs which are free of potentially inevitable repercussions that are associated with synthetic compounds. Therefore, the purpose of this review is to draw our attention to the potential therapeutic effects of various classes of natural compounds that target NRs such as phytochemicals, dietary components, venom constituents, royal jelly-derived compounds, and microbial derivatives in the establishment of novel and safe medications for cancer treatment. This review also emphasizes molecular mechanisms and signaling pathways that are leveraged to promote the anti-cancer effects of these natural compounds. We have also critically reviewed and assessed the advantages and limitations of current preclinical and clinical studies on this subject for cancer prophylaxis. This might subsequently pave the way for new paradigms in the discovery of drugs that target specific cancer types.

Mesenchymal stem cell-derived rapid drug screening system for Alzheimer's disease for the identification of novel drugs.

A reliable and efficient in vitro model is needed to screen drugs for Alzheimer's disease (AD), as many drugs are currently in the developmental stage. To address this, we developed an in vitro model using amniotic membrane-derived mesenchymal stem cells (AM-MSCs) to screen novel drugs for AD. We differentiated AM-MSCs into neurons and degenerated them using beta amyloid1-42 (Aß). We then tested AD drugs, which are commercially available such as donepezil, rivastigmine, memantine, citicoline, and two novel drugs, that is, probucol, an anti-hyperlipidaemic drug, and NMJ-2, a cinnamic acid analogue for their potential to protect the cells against neurodegeneration. We used gene expression and immunofluorescence staining to assess the neuroprotective ability of these drugs. We also measured the ability of these drugs to reduce lactate dehydrogenase, reactive oxygen species, and nitric oxide levels, as well as their ability to stabilize the mitochondrial membrane potential and increase acetylcholine (ACh) levels. The AD drugs and novel drugs reduced cytotoxicity and oxidative stress, stabilized mitochondrial membrane potential, and restored ACh levels. Furthermore, they reduced BACE1 expression, with a concomitant increase in the expression of cholinergic markers. This AM-MSCs-based AD-like model has immense potential to be an accurate human model and an alternative to animal models for testing a large number of lead compounds in a short time. Our results also suggest that the novel drugs probucol and NMJ-2 may protect against Aß-induced neurodegeneration.

The multidimensional role of the Wnt/ß-catenin signaling pathway in human malignancies.

Several signaling pathways have been identified as important for developmental processes. One of such important cascades is the Wnt/ß-catenin signaling pathway, which can regulate various physiological processes such as embryonic development, tissue homeostasis, and tissue regeneration; while its dysregulation is implicated in several pathological conditions especially cancers. Interestingly, deregulation of the Wnt/ß-catenin pathway has been reported to be closely associated with initiation, progression, metastasis, maintenance of cancer stem cells, and drug resistance in human malignancies. Moreover, several genetic and experimental models support the inhibition of the Wnt/ß-catenin pathway to answer the key issues related to cancer development. The present review focuses on different regulators of Wnt pathway and how distinct mutations, deletion, and amplification in these regulators could possibly play an essential role in the development of several cancers such as colorectal, melanoma, breast, lung, and leukemia. Additionally, we also provide insights on diverse classes of inhibitors of the Wnt/ß-catenin pathway, which are currently in preclinical and clinical trial against different cancers.

Netrin-like domain of sFRP4, a Wnt antagonist inhibits stemness, metastatic and invasive properties by specifically blocking MMP-2 in cancer stem cells from human glioma cell line U87MG.

Rapid proliferation, high stemness potential, high invasiveness and apoptotic evasion are the distinctive hallmarks of glioma malignancy. The dysregulation of the Wnt/ß-catenin pathway is the key factor regulating glioma malignancy. Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), which has a prominent pro-apoptotic role in glioma stem cells, has two functional domains, the netrin-like domain (NLD), and cysteine-rich domain (CRD) both of which contribute to apoptotic properties of the whole protein. However, there are no reports elucidating the specific effects of individual domains of sFRP4 in inhibiting the invasive properties of glioma. This study explores the efficacy of the domains of sFRP4 in inhibiting the key hallmarks of glioblastoma such as invasion, metastasis, and stemness. We overexpressed sFRP4 and its domains in the glioblastoma cell line, U87MG cells and observed that both CRD and NLD domains played prominent roles in attenuating cancer stem cell properties. Significantly, we could demonstrate for the first time that both NLD and CRD domains negatively impacted the key driver of metastasis and migration, the matrix metalloproteinase-2 (MMP-2). Mechanistically, compared to CRD, NLD domain suppressed MMP-2 mediated invasion more effectively in glioma cells as observed in matrigel invasion assay and a function-blocking antibody assay. Fluorescent matrix degradation assay further revealed that NLD reduces matrix degradation. NLD also significantly disrupted fibronectin assembly and decreased cell adhesion in another glioma cell line LN229. In conclusion, the NLD peptide of sFRP4 could be a potent short peptide therapeutic candidate for targeting MMP-2-mediated invasion in the highly malignant glioblastoma multiforme.

Aberrant lipid metabolism as an emerging therapeutic strategy to target cancer stem cells.

Emerging evidence in cancer metabolomics has identified reprogrammed metabolic pathways to be a major hallmark of cancer, among which deregulated lipid metabolism is a prominent field receiving increasing attention. Cancer stem cells (CSCs) comprise <0.1% of the tumor bulk and possess high self-renewal, tumor-initiating properties, and are responsible for therapeutic resistance, disease recurrence, and tumor metastasis. Hence, it is imperative to understand the metabolic rewiring occurring in CSCs, especially their lipid metabolism, on which there have been recent reports. CSCs rely highly upon lipid metabolism for maintaining their stemness properties and fulfilling their biomass and energy demands, ultimately leading to cancer growth and invasion. Hence, in this review we will shed light on the aberrant lipid metabolism that CSCs exploit to boost their survival, which comprises upregulation in de novo lipogenesis, lipid droplet synthesis, lipid desaturation, and ß-oxidation. Furthermore, the metabolic regulators involved in the process, such as key lipogenic enzymes, are also highlighted. Finally, we also summarize the therapeutic strategies targeting the key regulators involved in CSCs' lipid metabolism, which thereby demonstrates the potential to develop powerful and novel therapeutics against the CSC lipid metabolome.

Computational screening of dual inhibitors from FDA approved antiviral drugs on SARS-CoV-2 spike protein and the main protease using molecular docking approach.

The deadly disease-causing novel coronavirus has recently swept across the world and endangered many human lives. Although, various research on therapeutic measures to solve this pandemic crisis has been published; no favourable results have been achieved. We propose the use of potential FDA-approved dual inhibitors which can inhibit two targets (either on entry-level or the main protease) for the effective treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We screened 12 FDA-approved antiviral inhibitors listed in Drug bank and analysed the ADMET properties of each drug of interest to study the bioavailability, safety and toxicity. Two potential targets, the spike protein and the main protease of SARS-CoV-2 obtained from PDB have been used for molecular docking. All the selected drugs were docked with both targets and demonstrated strong hydrogen bond (HB) interactions in multiple active sites. Amongst these, the range of binding energy was from 3-7 kcal/mol for spike protein and 2-8 kcal/mol for the main protease. Upon comparison of all the processed drugs ganciclovir and zanamivir displayed significant binding energy with HB interactions with both, spike (-9.2 and -9 kcal/mol respectively) and the main protease (-9 kcal/mol). Ribavirin and tenofovir showed significant binding energy above -8 kcal/mol with seven HB interactions with the main protease and also spike protein. The novel findings regarding the antiviral properties of these dual inhibitors using a computational approach will be a good starting point for the efficacy determination of these drugs for pre-clinical and clinical studies aimed at developing active antivirals to target SARS-CoV-2. Keywords: SARS-CoV-2; FDA-approved drugs; viral inhibitors; in-silico analysis; molecular docking.

Secreted frizzled related proteins: Implications in cancers.

The Wnt (wingless-type) signaling pathway plays an important role in embryonic development, tissue homeostasis, and tumor progression becaluse of its effect on cell proliferation, migration, and differentiation. Secreted frizzled-related proteins (SFRPs) are extracellular inhibitors of Wnt signaling that act by binding directly to Wnt ligands or to Frizzled receptors. In recent years, aberrant expression of SFRPs has been reported to be associated with numerous cancers. As gene expression of SFRP members is often lost through promoter hypermethylation, inhibition of methylation through the use of epigenetic modifying agents could renew the expression of SFRP members and further antagonize deleterious Wnt signaling. Several reports have described epigenetic silencing of these Wnt signaling antagonists in various human cancers, suggesting their possible role as tumor suppressors. SFRP family members thus come across as potential tools in combating Wnt-driven tumorigenesis. However, little is known about SFRP family members and their role in different cancers. This review comprehensively covers all the available information on the role of SFRP molecules in various human cancers.

Generation of islet-like cell aggregates from human non-pancreatic cancer cell lines.

To explore a novel source for the derivation of islets, we examined the differentiation potential of human non-pancreatic cancer cell lines, HeLa (cervical carcinoma cell line) and MCF-7 (breast cancer cell line). These cells were subjected to a serum-free, three-step sequential differentiation protocol which gave two distinct cell populations: single cells and cellular aggregates. Subsequent analysis confirmed their identity as pancreatic acinar cells and islet-like cell aggregates (ICAs), as evidenced by amylase secretion and diphenylthiocarbazone staining respectively. Reverse transcriptase-PCR and immunocytochemistry assessment of the ICAs revealed the expression of pancreatic specific markers Ngn-3, Glut-2, Pax-6 and Isl-1. These ICAs secreted insulin in response to glucose challenge, confirming their functionality. We propose that ICAs generated from HeLa and MCF-7 cell lines could form a promising in vitro platform of human islet equivalents (hIEQs) for diabetes research.

miRNA on the Battlefield of Cancer: Significance in Cancer Stem Cells, WNT Pathway, and Treatment.

Carcinogenesis is a complex process characterized by intricate changes in organ histology, biochemistry, epigenetics, and genetics. Within this intricate landscape, cancer stem cells (CSCs) have emerged as distinct cell types possessing unique attributes that significantly contribute to the pathogenesis of cancer. The WNT signaling pathway plays a critical role in maintaining somatic stem cell pluripotency. However, in cancer, overexpression of WNT mediators enhances the activity of ß-catenin, resulting in phenomena such as recurrence and unfavorable survival outcomes. Notably, CSCs exhibit heightened WNT signaling compared to bulk cancer cells, providing intriguing insights into their functional characteristics. MicroRNAs (miRNAs), as post-transcriptional gene expression regulators, modulate various physiological processes in numerous diseases including cancer. Upregulation or downregulation of miRNAs can affect the production of pro-oncogenic or anti-oncogenic proteins, influencing cellular processes that maintain tissue homeostasis and promote either apoptosis or differentiation, even in cancer cells. In order to understand the dysregulation of miRNAs, it is essential to examine miRNA biogenesis and any possible alterations at each step. The potential of a miRNA as a biomarker in prognosis, diagnosis, and detection is being assessed using technologies such as next-generation sequencing. Extensive research has explored miRNA expression profiles in cancer, leading to their utilization as diagnostic tools and the development of personalized and targeted cancer therapies. This review delves into the role of miRNAs in carcinogenesis in relation to the WNT signaling pathway along with their potential as druggable compounds.

An Overview of Ovarian Cancer: The Role of Cancer Stem Cells in Chemoresistance and a Precision Medicine Approach Targeting the Wnt Pathway with the Antagonist sFRP4.

Ovarian cancer is one of the most prevalent gynecological cancers, having a relatively high fatality rate with a low five-year chance of survival when detected in late stages. The early detection, treatment and prevention of metastasis is pertinent and a pressing research priority as many patients are diagnosed only in stage three of ovarian cancer. Despite surgical interventions, targeted immunotherapy and adjuvant chemotherapy, relapses are significantly higher than other cancers, suggesting the dire need to identify the root cause of metastasis and relapse and present more precise therapeutic options. In this review, we first describe types of ovarian cancers, the existing markers and treatment modalities. As ovarian cancer is driven and sustained by an elusive and highly chemoresistant population of cancer stem cells (CSCs), their role and the associated signature markers are exhaustively discussed. Non-invasive diagnostic markers, which can be identified early in the disease using circulating tumor cells (CTCs), are also described. The mechanism of the self-renewal, chemoresistance and metastasis of ovarian CSCs is regulated by the Wnt signaling pathway. Thus, its role in ovarian cancer in promoting stemness and metastasis is delineated. Based on our findings, we propose a novel strategy of Wnt inhibition using a well-known Wnt antagonist, secreted frizzled related protein 4 (sFRP4), wherein short micropeptides derived from the whole protein can be used as powerful inhibitors. The latest approaches to early diagnosis and novel treatment strategies emphasized in this review will help design precision medicine approaches for an effective capture and destruction of highly aggressive ovarian cancer.

iPSC-Derived Glioblastoma Cells Have Enhanced Stemness Wnt/ß-Catenin Activity Which Is Negatively Regulated by Wnt Antagonist sFRP4.

Growing evidence indicates that cancer stem cells (CSCs) endow the tumor with stem-like properties. Recently, induced pluripotent stem cells (iPSCs) have gained increased attention because of their easy derivation and availability and their potential to differentiate into any cell type. A CSC model derived from iPSCs of human origin would help understand the driving force of tumor initiation and early progression. We report the efficient generation of feeder-free SSEA4, TRA-1-60 and TRA-1-81 positive iPSCs from amniotic membrane-derived mesenchymal stem cells (AMMSCs), which successfully differentiated into three germ layers. We then developed human iPSC-derived glioblastoma multiforme (GBM) model using conditioned media (CM) from U87MG cell line and CSCs derived from U87MG, which confer iPSCs with GBM and GSC-like phenotypes within five days. Both cell types overexpress MGMT and GLI2, but only GSCs overexpress CD133, CD44, ABCG2 and ABCC2. We also observed overexpression of LEF1 and ß-catenin in both cell types. Down-regulation of Wnt antagonist secreted frizzled-related protein 4 (sFRP4) in GBM and GSCs, indicating activation of the Wnt/ß-catenin pathway, which could be involved in the conversion of iPSCs to CSCs. From future perspectives, our study will help in the creation of a rapid cell-based platform for understanding the complexity of GBM.

Want of Wnt in Parkinson's disease: Could sFRP disrupt interplay between Nurr1 and Wnt signaling?

Nuclear receptor related 1 (Nurr1) is a transcription factor known to regulate the development and maintenance of midbrain dopaminergic (mDA) neurons. Reports have confirmed that defect or obliteration of Nurr1 results in neurodegeneration and motor function impairment leading to Parkinson's disease (PD). Studies have also indicated that Nurr1 regulates the expression of alpha-synuclein (α-SYN) and mutations in Nurr1 cause α-SYN overexpression, thereby increasing the risk of PD. Nurr1 is modulated via various pathways including Wnt signaling pathway which is known to play an important role in neurogenesis, and deregulation of it contributes to PD pathogenesis. Both Wnt/ß-catenin dependent and independent pathways are implicated in the activation of Nurr1 and subsequent downregulation of α-SYN. This review highlights the interaction between Nurr1 and Wnt signaling pathways in mDA neuronal development. We further hypothesize how modulation of Wnt signaling pathway by its antagonist, secreted frizzled related proteins (sFRPs) could be a potential route to treat PD.

Identification of a Novel Wnt Antagonist Based Therapeutic and Diagnostic Target for Alzheimer's Disease Using a Stem Cell-Derived Model.

Currently, all the existing treatments for Alzheimer's disease (AD) fail to stall progression due to longer duration of time between onset of the symptoms and diagnosis of the disease, raising the necessity of effective diagnostics and novel treatment. Specific molecular regulation of the onset and progression of disease is not yet elucidated. This warranted investigation of the role of Wnt signaling regulators which are thought to be involved in neurogenesis. The AD model was established using amyloid beta (Aß) in human mesenchymal stem cells derived from amniotic membranes which were differentiated into neuronal cell types. In vivo studies were carried out with Aß or a Wnt antagonist, AD201, belonging to the sFRP family. We further created an AD201-knockdown in vitro model to determine the role of Wnt antagonism. BACE1 upregulation, ChAT and α7nAChR downregulation with synapse and functionality loss with increases in ROS confirmed the neurodegeneration. Reduced ß-catenin and increased AD201 expression indicated Wnt/canonical pathway inhibition. Similar results were exhibited in the in vivo study along with AD-associated behavioural and molecular changes. AD201-knockdown rescued neurons from Aß-induced toxicity. We demonstrated for the first time a role of AD201 in Alzheimer's disease manifestation, which indicates a promising disease target and biomarker.

Short peptide domains of the Wnt inhibitor sFRP4 target ovarian cancer stem cells by neutralizing the Wnt ß-catenin pathway, disrupting the interaction between ß-catenin and CD24 and suppressing autophagy.

AIMS: One of the hallmarks of cancer stem cells (CSC) is hyperactive Wnt ß-catenin signaling due to the decreased presence of Wnt antagonists such as secreted frizzled related protein 4 (SFRP4). Cysteine-rich domain (CRD) and netrin-like domain (NLD) are the two functional domains of SFRP4 having anti-tumor properties. In this study, we have explored the effectiveness of short micropeptides SC-301 (from CRD) and SC-401 (from NLD) on CSC properties, EMT, apoptosis and autophagy in ovarian CSCs enriched from PA-1 and SKOV-3 cell lines. MAIN METHODS: Gene expression analysis, Western blot and immunocytochemistry were performed on ovarian CSCs to evaluate the inhibitory potential of micropeptides to various CSC associated oncogenic properties. Co-immunoprecipitation was performed to detect the binding of CD24 to ß-catenin protein complex. CYTO-ID Autophagy Detection Kit 2.0 was used to monitor autophagic flux in peptide treated CSCs. KEY FINDINGS: It is clearly seen that the micropeptides derived from both the domains inhibit Wnt pathway, initiate apoptosis, inhibit migration and chemosensitize CSCs. Specifically, CD24, a defining marker of ovarian CSC was suppressed by peptide treatment. Notably, interaction between CD24 and ß-catenin was disrupted upon peptide treatment. SFRP4 peptide treatment also suppressed the autophagic process which is crucial for CSC survival. SIGNIFICANCE: The study demonstrated that although both peptides have inhibitory effects, SC-401 was emphatically more effective in targeting CSC properties and down regulating the Wnt ß-catenin machinery.

Unwinding the role of Wnt signaling cascade and molecular triggers of motor neuron degeneration in amyotrophic lateral sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative condition, triggered by various factors causing the degeneration of upper and lower motor neurons, resulting in progressive muscle wasting, paralysis, and death. Multiple in vivo and in vitro models have been established to unravel the molecular events leading to the deterioration of motor neurons in ALS. The canonical and non-canonical Wnt signaling pathway has been implicated to play a crucial role in the progression of neurodegenerative disorders. This review discusses the role of Wnt signaling in the reported causes of ALS such as oxidative stress, mitochondrial dysfunction, autophagy, and apoptosis. Mutations in ALS-associated genes such as SOD1, C9orf72, TDP43, FUS, and OPTN cause an imbalance in neuronal integrity and homeostasis leading to motor neuron demise. Wnt signaling is also observed to play a crucial role in the muscle sparing of oculomotor neurons. The non-canonical Wnt/Ca2+ pathway which regulates intrinsic electrophysiological properties and mobilizes calcium ions to maintain neuronal integrity has been found to be altered in the stem cell-derived ALS model. Thus, the interplay of dysregulated canonical and non-canonical Wnt pathways in multiple motor neuron disease models has shown that Wnt contributes to disease progression indicating it to be utilized as a potential target for ALS.

Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence.

Ovarian cancers are tumors that originate from the different cells of the ovary and account for almost 4% of all the cancers in women globally. More than 30 types of tumors have been identified based on the cellular origins. Epithelial ovarian cancer (EOC) is the most common and lethal type of ovarian cancer which can be further divided into high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous carcinoma. Ovarian carcinogenesis has been long attributed to endometriosis which is a chronic inflammation of the reproductive tract leading to progressive accumulation of mutations. Due to the advent of multi-omics datasets, the consequences of somatic mutations and their role in altered tumor metabolism has been well elucidated. Several oncogenes and tumor suppressor genes have been implicated in the progression of ovarian cancer. In this review, we highlight the genetic alterations undergone by the key oncogenes and tumor suppressor genes responsible for the development of ovarian cancer. We also summarize the role of these oncogenes and tumor suppressor genes and their association with a deregulated network of fatty acid, glycolysis, tricarboxylic acid and amino acid metabolism in ovarian cancers. Identification of genomic and metabolic circuits will be useful in clinical stratification of patients with complex etiologies and in identifying drug targets for personalized therapies against cancer.