Sharma, UttamMurmu, MasangBarwal, Tushar SinghTuli, Hardeep SinghJain, ManjuPrakash, HridayeshKaceli, TeaJain, AklankBishayee, Anupam2024-01-162024-08-132024-01-162024-08-132022-03-281718772910.3390/curroncol29040189https://doi.org/10.3390/curroncol29040189http://10.2.3.109/handle/32116/2871Despite the availability of modern techniques for the treatment of esophageal squamous cell carcinoma (ESCC), tumor recurrence and metastasis are significant challenges in clinical management. Thus, ESCC possesses a poor prognosis and low five-year overall survival rate. Notably, the origin and recurrence of the cancer phenotype are under the control of complex cancer-related signaling pathways. In this review, we provide comprehensive knowledge about long non-coding RNAs (lncRNAs) related to Wnt/?-catenin and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ESCC and its implications in hindering the efficacy of chemotherapeutic drugs. We observed that a pool of lncRNAs, such as HERES, TUG1, and UCA1, associated with ESCC, directly or indirectly targets various molecules of the Wnt/?-catenin pathway and facilitates the manifestation of multiple cancer phenotypes, including proliferation, metastasis, relapse, and resistance to anticancer treatment. Additionally, several lncRNAs, such as HCP5 and PTCSC1, modulate PI3K/Akt/mTOR pathways during the ESCC pathogenesis. Furthermore, a few lncRNAs, such as AFAP1-AS1 and LINC01014, block the efficiency of chemotherapeutic drugs, including cisplatin, 5-fluorouracil, paclitaxel, and gefitinib, used for ESCC treatment. Therefore, this review may help in designing a better therapeutic strategy for ESCC patients. � 2022 by the authors. Licensee MDPI, Basel, Switzerland.en-USchemotherapyesophageal squamous cell carcinomalong non-coding RNAsPI3K/Akt/mTORsignaling pathwaysWnt/?-cateninReview