Therapeutic Target In Human Cancer Research Articles

A comprehensive analysis of the pyruvate kinase M1/2 (PKM) in human cancer.

Pyruvate Kinase Muscle Isozyme (PKM), as a member of the pyruvate kinase, is a key enzyme in glycolysis. Numerous tumors have demonstrated its oncogenic properties. There is, however, no pan-carcinogenic analysis for PKM. A thorough analysis of PKM across various types of cancer was carried out using bioinformatics resources like The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) database. This study involved analyzing the role of PKM in 33 various types of cancers, along with investigating gene expressions, survival rates, clinical importance, genetic changes, immune system presence, and related signaling pathways. Furthermore, we evaluated the effects of PKM knockdown on human colon carcinoma, and glioblastoma cell lines by in vitro experimentation. In most tumors, PKM expression was markedly increased and was associated with unfavorable overall survival (OS) in certain individuals. In addition, infiltration of macrophages was associated with PKM expression in various tumors. PKM was linked to glycolysis/gluconeogenesis, HIF-1 signaling, carbon metabolism, and NADPH regeneration in a mechanistic manner. Additionally, cell experiments showed that the knockdown of PKM could reduce the proliferation and migration abilities while promoting the apoptosis of Caco-2, and U-87 MG cells. PKM controls immune cell infiltration, impacts patient outcomes in various types of cancer, and plays an essential role in proliferation and migration in some tumor cells by affecting glycometabolism. The PKM molecule may serve as a potential prognostic biomarker and therapeutic target for human cancers.

LncRNA HOXA10-AS as a novel biomarker and therapeutic target in human cancers.

Long non-coding RNAs (lncRNAs) are crucial regulatory molecules that participate in numerous cellular development processes, and they have gathered much interest recently. HOXA10 antisense RNA (HOXA10-AS, also known as HOXA-AS4) is a novel lncRNA that was identified to be dysregulated in some prevalent malignancies. In this review, the clinical significance of HOXA10-AS for the prognosis of various cancers is analyzed. In addition, the major advances in our understanding of the cellular biological functions and mechanisms of HOXA10-AS in different human cancers are summarized. These cancers include esophageal carcinoma (ESCA), gastric cancer (GC), glioma, laryngeal squamous cell carcinoma (LSCC), acute myeloid leukemia (AML), lung adenocarcinoma (LUAD), nasopharyngeal carcinoma (NPC), oral squamous cell carcinoma (OSCC), and pancreatic cancer. We also note that the aberrant expression of HOXA10-AS promotes malignant progression through various underlying mechanisms. In conclusion, HOXA10-AS is expected to serve as an ideal clinical biomarker and an effective cancer therapy target.

Nuclear translocation of RON receptor tyrosine kinase. New mechanistic and functional insights.

Receptor tyrosine kinases (RTKs) are membrane sensors that monitor alterations in the extracellular milieu and translate this information into appropriate cellular responses. Epidermal growth factor receptor (EGFR) is the most well-known model in which gene expression is upregulated by mitogenic signals through the activation of multiple signaling cascades or by nuclear translocation of the full-length EGFR protein. RON (Receptuer d'Origine Nantatise, also known as macrophage stimulating 1 receptor, MST1R) has recently gained attention as a therapeutic target for human cancer. This review summarizes the recent understanding of the unusual nuclear translocation of uncleaved RON receptor proteins in response to cellular stresses, such as serum starvation, hormonal deprivation, hypoxia, and genotoxicity. This nonligand mechanism, achieved by RON per se or by interaction with EGFR, may directly activate the transcriptional machinery necessary for cancer cells to survive. In vitro experiments have demonstrated the importance of tyrosine kinase of RON in binding to and activating the c-JUN promoter, HIF-1α, DNA helicase 2, DNA-dependent protein kinase catalytic subunit, and other stress-responsive networks. Nuclear RON-activated nonhomologous end joining repair confers chemoresistance to drugs that induce double-strand breaks (DSBs) in cancer cells. Tyrosine kinase inhibitors or monoclonal antibodies targeting RON kinase may therefore be useful treatments for patients with RON-overexpressing tumors. DSB-inducing anticancer drugs are not recommended for these cancer patients. Moreover, multi-RTK inhibition is a more rational strategy for patients with RON- and RTK-coexpressing human cancer.

Emerging roles of angiopoietin‑like 4 in human tumors (Review).

Angiopoietin‑like 4 (ANGPTL4), a member of the angiopoietin family, plays critical roles in angiogenesis, lipid metabolism and inflammation. It has been demonstrated that ANGPTL4 has significant influence on various diseases. Accumulating evidence has highlighted the impacts of ANGPTL4 on human malignancies. ANGPTL4 is commonly overexpressed in various types of cancer, such as breast, non‑small cell lung, gastric and colorectal cancer. Its upregulation promotes tumor growth, invasion, metastasis and angiogenesis, as well as metabolic reprogramming and resistance to programmed cell death, radiotherapy and chemotherapy. However, ANGPTL4 has also exhibited antitumor effects under certain conditions, indicating its complex roles in tumor biology. The transcriptional regulation of ANGPTL4 is influenced by multiple factors, such as HIF‑1, PPARs, TGF‑β and long non‑coding RNAs. In terms of signaling pathways, STATs, PI3K/AKT and COX-2/PGE2 are important in regulating cellular processes. The present review summarizes the biological functions of ANGPTL4 in tumors and its association with patient prognosis. Furthermore, the key molecular mechanisms and potential reasons for its dual roles in cancer are also discussed. In conclusion, ANGPTL4 is a valuable diagnostic biomarker and a potential therapeutic target for human cancers.

TRIB3 overexpression predicts malignant progression and poor prognosis in human solid tumors: bioinformatics validation and clinical significance

ABSTRACT Introduction Overexpression of tribbles homolog 3 (TRIB3) has been reported in various cancers, yet its clinical significance remains contentious. This study aims to elucidate the association between TRIB3 overexpression and the progression and prognosis of solid tumors. Methods A comprehensive analysis was conducted using data from published studies and The Cancer Genome Atlas (TCGA) up to May 2023. We evaluated the impact of high TRIB3 expression on tumor malignancy and survival outcomes across different cancer types. Results Seventeen studies met the inclusion criteria. Our findings revealed that TRIB3 overexpression is significantly associated with increased distant metastasis (OR = 4.01, 95% CI: 2.36–6.74, p < 0.001) and advanced histological stage (OR = 2.68, 95% CI: 1.50–4.78, p < 0.001). Additionally, high TRIB3 expression significantly elevated the risk of reduced overall survival (OS) in cancer patients (HR = 1.52, 95% CI: 1.05–2.20, p < 0.001), indicating a poor prognosis. Analyses of TCGA data among various prognostic indicators corroborated these findings. Conclusions TRIB3 overexpression is significantly linked to malignant progression and unfavorable prognosis in diverse solid tumors. These results suggest that TRIB3 holds promise as a biomarker and therapeutic target in human cancers.

EZH2: novel therapeutic target for human cancer

EZH2: novel therapeutic target for human cancer

LncRNAs'p potential roles in the pathogenesis of cancer via interacting with signaling pathways; special focus on lncRNA-mediated signaling dysregulation in lung cancer.

Lung cancer ranks among the most lethal types of cancer globally, with a high occurrence and fatality rate. The spread of cancer to other parts of the body, known as metastasis, is the primary cause of treatment failure and death in lung cancer cases. Current approaches for treating advanced lung cancer typically involve a combination of chemotherapy and targeted therapy. However, the majority of patients ultimately develop resistance to these treatments, leading to a worsened prognosis. In recent years, cancer biology research has predominantly focused on the role of protein-encoding genes in cancer development. Long non-coding RNAs (lncRNAs) are transcripts over 200 nucleotides in length that do not encode proteins but are crucial RNA molecules involved in numerous biological functions. While many functions of lncRNAs remain unknown, some have been linked to human diseases, including cancer. Studies have demonstrated that lncRNAs interact with other large molecules in the cell, such as proteins, DNA, and RNA, influencing various critical aspects of cancer. LncRNAs play a significant role in regulating gene expression and have a crucial function in the transcriptional regulation of cancer cells. They mediate various biological and clinical processes such as invasion, metastasis, apoptosis, and cell proliferation. Dysregulation of lncRNAs has been found to impact the process of carcinogenesis through advanced technologies like RNA sequencing and microarrays. Collectively, these long non-coding RNAs hold promise as potential biomarkers and therapeutic targets for human cancers. In this segment, we provide a comprehensive summary of the literature on the characteristics and formation of lncRNAs, along with an overview of their current known roles in lung cancer.

Molecular dynamics simulations provide insights into ULK-101 potency and selectivity toward autophagic kinases ULK1/2

Kinase domains are highly conserved within proteins in both sequence and structure. Many factors, including phosphorylation, amino acid substitutions or mutations, and small molecule inhibitor binding, influence conformations of the kinase domain and enzymatic activity. ULK1 and ULK2 are serine/threonine kinases that serve important roles in autophagy, an intracellular recycling process capable of degrading proteins and organelles via fusion with lysosomes. ULK1/2 are emerging as therapeutic targets in human cancer, particularly KRAS-driven malignancies. Here, we performed molecular dynamics (MD) simulations to hypothesize bound poses for the ULK1/2 small molecule inhibitor, ULK-101. We observed stable bound states for ULK-101 to the adenosine triphosphate (ATP)-binding site of ULK2, coordinated by hydrogen bonding with the hinge backbone and the catalytic lysine sidechain. Notably, ULK-101 occupies a hydrophobic pocket associated with the N-terminus of the αC-helix. Large movements in the phosphate-binding loop (P-loop) are also associated with ULK-101 inhibitor binding and exit from ULK2. Together, our data support a model to explain ULK-101 potency toward ULK1/2.

Discovery of MD-265: A Potent MDM2 Degrader That Achieves Complete Tumor Regression and Improves Long-Term Survival of Mice with Leukemia.

MDM2 has been pursued as an attractive therapeutic target for human cancers. Herein, we describe our discovery of MD-265 as a promising PROTAC MDM2 degrader and extensive in vitro and in vivo evaluations of its therapeutic potential and mechanism of action. MD-265 effectively depleted MDM2 protein in cancer cells at concentrations as low as 1 nM, leading to strong activation of p53 in cancer cells carrying wild-type p53. It selectively inhibited the growth of wild-type p53 leukemia cell lines and showed no activity in mutated p53 lines. MD-265 achieved persistent tumor regression in a leukemia xenograft model without causing any signs of toxicity and dramatically improved survival of mice in a disseminated leukemia model even with a weekly administration. MD-265 displayed an excellent intravenous PK profile in mice, rats, and dogs. MD-265 is a promising MDM2 degrader for advanced preclinical development for the treatment of human cancers.

PAK4 Is Involved in the Stabilization of PD-L1 and the Resistance to Doxorubicin in Osteosarcoma and Predicts the Survival of Diagnosed Patients.

PAK4 and PD-L1 have been suggested as novel therapeutic targets in human cancers. Moreover, PAK4 has been suggested to be a molecule closely related to the immune evasion of cancers. Therefore, this study evaluated the roles of PAK4 and PD-L1 in the progression of osteosarcomas in 32 osteosarcomas and osteosarcoma cells. In human osteosarcomas, immunohistochemical positivity for the expression of PAK4 (overall survival, p = 0.028) and PD-L1 (relapse-free survival, p = 0.002) were independent indicators for the survival of patients in a multivariate analysis. In osteosarcoma cells, the overexpression of PAK4 increased proliferation and invasiveness, while the knockdown of PAK4 suppressed proliferation and invasiveness. The expression of PAK4 was associated with the expression of the molecules related to cell cycle regulation, invasion, and apoptosis. PAK4 was involved in resistance to apoptosis under a treatment regime with doxorubicin for osteosarcoma. In U2OS cells, PAK4 was involved in the stabilization of PD-L1 from ubiquitin-mediated proteasomal degradation and the in vivo infiltration of immune cells such as regulatory T cells and PD1-, CD4-, and CD8-positive cells in mice tumors. In conclusion, this study suggests that PAK4 is involved in the progression of osteosarcoma by promoting proliferation, invasion, and resistance to doxorubicin and stabilized PD-L1 from proteasomal degradation.

EV20/Omomyc: A novel dual MYC/HER3 targeting immunoconjugate

MYC is one of the most important therapeutic targets in human cancer. Many attempts have been made to develop small molecules that could be used to curb its activity in patients, but most failed to identify a suitable direct inhibitor. After years of preclinical characterization, a tissue-penetrating peptide MYC inhibitor, called Omomyc, has been recently successfully used in a Phase I dose escalation study in late-stage, all-comers solid tumour patients. The study showed drug safety and positive signs of clinical activity, prompting the beginning of a new Phase Ib combination study currently ongoing in metastatic pancreatic adenocarcinoma patients. In this manuscript, we have explored the possibility to improve Omomyc targeting to specific cancer subtypes by linking it to a therapeutic antibody. The new immunoconjugate, called EV20/Omomyc, was developed by linking a humanised anti-HER3 antibody, named EV20, to Omomyc using a bifunctional linker. EV20/Omomyc shows antigen-dependent penetrating activity and therapeutic efficacy in a metastatic model of neuroblastoma. This study suggests that directing Omomyc into specific cell types using antibodies recognising tumour antigens could improve its therapeutic activity in specific indications, like in the paediatric setting.

Discovery of PRMT3 Degrader for the Treatment of Acute Leukemia.

Protein arginine methyltransferase 3 (PRMT3) plays an important role in gene regulation and a variety of cellular functions, thus, being a long sought-after therapeutic target for human cancers. Although a few PRMT3 inhibitors are developed to prevent the catalytic activity of PRMT3, there is little success in removing the cellular levels of PRMT3-deposited ω-NG,NG-asymmetric dimethylarginine (ADMA) with small molecules. Moreover, the non-enzymatic functions of PRMT3 remain required to be clarified. Here, the development of a first-in-class MDM2-based PRMT3-targeted Proteolysis Targeting Chimeras (PROTACs) 11 that selectively reduced both PRMT3 protein and ADMA is reported. Importantly, 11 inhibited acute leukemia cell growth and is more effective than PRMT3 inhibitor SGC707. Mechanism study shows that 11 induced global gene expression changes, including the activation of intrinsic apoptosis and endoplasmic reticulum stress signaling pathways, and the downregulation of E2F, MYC, oxidative phosphorylation pathways. Significantly, the combination of 11 and glycolysis inhibitor 2-DG has a notable synergistic antiproliferative effect by further reducing ATP production and inducing intrinsic apoptosis, thus further highlighting the potential therapeutic value of targeted PRMT3 degradation. These data clearly demonstrated that degrader 11 is a powerful chemical tool for investigating PRMT3 protein functions.

Discovery of Potent and Selective G9a Degraders for the Treatment of Pancreatic Cancer.

G9a, which was initially identified as a histone H3 Lys9 (H3K9) methyltransferase, is potentially an attractive therapeutic target for human cancers. Despite its importance, there is no available selective G9a chemical probe because its homologous protein GLP shares approximately 80% of its sequence with G9a. The development of G9a chemical probes with high selectivity for G9a over GLP is a big challenge but is extremely valuable for understanding G9a-related biology. Herein, we developed a first-in-class selective G9a degrader G9D-4, which induced a dose- and time-dependent G9a degradation without degradation of GLP. G9D-4 exhibited effective antiproliferative activities in a panel of pancreatic cancer cell lines and was able to sensitize KRASG12D mutant pancreatic cancer cells to KRASG12D inhibitor MRTX1133. These data clearly demonstrated the practicality and importance of a selective G9a degrader as a preliminary chemical probe suitable for understanding G9a-related biology and a promising strategy for the treatment of pancreatic cancer.

Integrated Bioinformatics Analysis and Transcriptomics Analysis Predict Jumonji and AT Rich Interacting Domain2 (JARID2) as a Therapeutic Target in Human Cancers

Integrated Bioinformatics Analysis and Transcriptomics Analysis Predict Jumonji and AT Rich Interacting Domain2 (JARID2) as a Therapeutic Target in Human Cancers

Pan-cancer analysis combined with experiments predicts NNMT as a therapeutic target for human cancers

The identification of effective therapeutic targets plays a pivotal role in advancing cancer treatment outcomes. We employed a comprehensive pan-cancer analysis, complemented by experimental validation, to explore the potential of Nicotinamide N-methyltransferase (NNMT) as a promising therapeutic strategy for human cancers. By analyzing large-scale transcriptomic datasets across various cancer types, we consistently observed upregulated expression of NNMT. Furthermore, elevated NNMT expression correlated with inferior overall survival in multiple cancer cohorts, underscoring its significance as a prognostic biomarker. Additionally, we investigated the relationship between NNMT expression and the tumor immune microenvironment, which plays a crucial role in regulating anti-tumor immune responses. To confirm the malignant functions of NNMT in tumor cells, we conducted a series of cell-based experiments, revealing that NNMT promotes cancer cell proliferation and invasion, indicative of its oncogenic properties. The integration of computational analysis and experimental validation in our study firmly establishes NNMT as a potential therapeutic target for human cancers. Specifically, targeting NNMT holds promise for the development of innovative and effective cancer treatments. Further investigations into NNMT's role in cancer pathogenesis could potentially pave the way for groundbreaking advancements in cancer treatment.

LncRNA TUG1 and its Molecular Mechanisms in Human Cancer.

As lncRNAs have increasingly been investigated, they are no longer simply defined as RNAs with no transcription capability. Studies have identified significant associations between the abnormal expression of lncRNAs and human diseases, particularly the mechanisms by which lncRNAs play a part in cancers, which are of considerable attention to researchers. As a result of the complex spatial structure, the mechanisms of interaction of lncRNAs in cancer cells are also complicated and diversified. Among a series of lncRNAs, TUG1, which is now considered to be a very high-value lncRNA, has recently been identified to express abnormally in some malignancies, leading to different alterations in cancer cells proliferation, migration, invasion, apoptosis, and drug resistance, and hence promoting or inhibiting cancer progression. Current studies have implicitly indicated that TUG1 can be used as a therapeutic target for human cancers. However, the biological functions of TUG1 have been studied for a short period of time, and the complete molecular mechanism still needs to be clarified. Accordingly, this review focuses on the principal molecular mechanisms of TUG1 in human cancers and the specific mechanisms of action in different cancer development processes based on existing studies.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

Abstract 5912: Rational design of a small-molecule inhibitor targeting the allosteric site of sos1 in oncogenic k-ras pancreatic cancer

Abstract Oncogenic Kras signaling is a key therapeutic target in human cancers. Ras activation is catalyzed by guanine nucleotide exchange factors (GEFs), of which SOS1 is a major player that transduces receptor tyrosine kinase signaling to Ras. In addition to recently devised oncogenic Kras targeting small molecule inhibitors, disrupting the catalytic interaction between Ras and SOS1 has emerged as an attractive therapeutic strategy in working synergistically with Kras inhibitors and overcoming resistance. Previous studies have demonstrated an active “feed forward” loop of active Kras binding to the allosteric site of SOS1 that further stimulates SOS1 catalytic activation of wild type H/N/Kras, which is required for oncogenic Kras driven tumorigenesis. Here we have developed a rational approach that combines virtual screening with experimental screening to identify small molecule inhibitors that target the allosteric site of SOS1 to suppress oncogenic Kras mediated SOS1-regulated wild-type Ras activities. Unlike SOS1 catalytic site inhibitors which can have significant toxicity due to their ability to inhibit normal Ras signaling function, the lead SOS1 allosteric inhibitors developed in our laboratory binds to the allosteric site of SOS1 and blocks active Ras interaction with SOS1: we found these inhibitors can competitively suppresses SOS1-Ras interaction at the SOS1 allosteric site and dose-dependently inhibits the feed-forward SOS1 GEF activity. Mutagenesis and structure-activity relationship studies mapped the site of action to the SOS1 allosteric site, and preliminarily defined the chemical moieties in the inhibitor essential for the activity. The inhibitor showed dose-dependent and selective efficacy in inhibiting WT Ras activity, downstream signaling activities, and associated cell proliferation in KRAS mutation cells but not KRAS wild-type cells. Compared to the SOS1 catalytic inhibitor, BI3406, our inhibitors showed better selectivity for KRAS mutant pancreatic cancer cells vs. WT KRAS cells. These studies establish a proof of principle for the rational design of small molecule inhibitors targeting an oncogenic Kras specific allosteric site of SOS1 and provide a novel therapeutic concept to target KRAS-driven tumors more effectively. Citation Format: Xin Duan, Chris R Evelyn, Jacek Biesiada, James F Johnson, William L. Seibel, Jaroslaw Meller, Yi Zheng. Rational design of a small-molecule inhibitor targeting the allosteric site of sos1 in oncogenic k-ras pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5912.

Pan-cancer integrated analysis of ANKRD1 expression, prognostic value, and potential implications in cancer

There is substantial evidence demonstrating the crucial role of inflammation in oncogenesis. ANKRD1 has been identified as an anti-inflammatory factor and is related to tumor drug resistance. However, there have been no studies investigating the prognostic value and molecular function of ANKRD1 in pan-cancer. In this study, we utilized the TCGA, GTEx, GSCALite, ENCORI, CTRP, DAVID, AmiGO 2, and KEGG databases as well as R language, to explore and visualize the role of ANKRD1 in tumors. We employed the ROC curve to explore its diagnostic significance, while the Kaplan–Meier survival curve and Cox regression analysis were used to investigate its prognostic value. Additionally, we performed Pearson correlation analysis to evaluate the association between ANKRD1 expression and DNA methylation, immune cell infiltration, immune checkpoints, TMB, MSI, MMR, and GSVA. Our findings indicate that ANKRD1 expression is dysregulated in pan-cancer. The ROC curve revealed that ANKRD1 expression is highly sensitive and specific in diagnosing CHOL, LUAD, LUSC, PAAD, SKCM, and UCS (AUC > 85.0%, P < 0.001). Higher ANKRD1 expression was related to higher overall survival (OS) in LGG, but with lower OS in COAD and STAD (P < 0.001). Moreover, Cox regression and nomogram analyzes suggested that ANKRD1 is an independent factor for COAD, GBM, HNSC, and LUSC. Dysregulation of ANKRD1 expression in pan-cancer involves DNA methylation and microRNA regulation. Using the CTRP database, we discovered that ANKRD1 may influence the half-maximal inhibitory concentration (IC50) of several anti-tumor drugs. ANKRD1 expression showed significant correlations with immune cell infiltration (including cancer-associated fibroblast and M2 macrophages), immune checkpoints, TMB, MSI, and MMR. Furthermore, ANKRD1 is involved in various inflammatory and immune pathways in COAD, GBM, and LUSC, as well as cardiac functions in HNSC. In vitro experiments demonstrated that ANKRD1 promotes migration, and invasion activity, while inhibiting apoptosis in colorectal cancer cell lines (Caco2, SW480). In summary, ANKRD1 represents a potential prognostic biomarker and therapeutic target in human cancers, particularly in COAD.

The interaction between lncRNAs and transcription factors regulating autophagy in human cancers: A comprehensive and therapeutical survey.

Autophagy, as a highly conserved cellular process, participates in cellular homeostasis by degradation and recycling of damaged organelles and proteins. Besides, autophagy has been evidenced to play a dual role through cancer initiation and progression. In the early stage, it may have a tumor-suppressive function through inducing apoptosis and removing damaged cells and organelles. However, late stages promote tumor progression by maintaining stemness features and induction of chemoresistance. Therefore, identifying and targeting molecular mechanisms involved in autophagy is a potential therapeutic strategy for human cancers. Multiple transcription factors (TFs) are involved in the regulation of autophagy by modulating the expression of autophagy-related genes (ATGs). In addition, a wide array of long noncoding RNAs (lncRNAs), a group of regulatory ncRNAs, have been evidenced to regulate the function of these autophagy-related TFs through tumorigenesis. Subsequently, the lncRNAs/TFs/ATGs axis shows great potential as a therapeutic target for human cancers. Therefore, this review aimed to summarize new findings about the role of lncRNAs in regulating autophagy-related TFs with therapeutic perspectives.