Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements

Akter, Salima; Rahman, Md. Ataur; Hasan, Mohammad Nazmul; Akhter, Hajara; Noor, Priya; Islam, Rokibul; Shin, Yoonhwa; Rahman, Md. Hasanur; Gazi, Md. Shamim; Huda, Md. Nazmul; Mai, Nguyen; Chung, Jinwook; Han, Sun-Hee; Kim, Bonglee; Kang, Insug; Ha, Joohun; Choe, Wonchae; Choi, Tae Gyu; Kim, Sung Soo

doi:10.3390/cells11040650

Cited by 38 publications

(21 citation statements)

References 172 publications

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“…OC is one of the most serious gynecological tumors and is a global public health problem. Treatment modalities for OC mainly include surgical debulking and radiotherapy or chemotherapy [ 4 ]. Because of drug resistance and the high rate of recurrence, treatment results are unsatisfactory.…”

Section: Discussionmentioning

confidence: 99%

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The Value of the Stemness Index in Ovarian Cancer Prognosis

Yuan

Pang

et al. 2022

Genes

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Ovarian cancer (OC) is one of the most common gynecological malignancies. It is associated with a difficult diagnosis and poor prognosis. Our study aimed to analyze tumor stemness to determine the prognosis feature of patients with OC. At this job, we selected the gene expression and the clinical profiles of patients with OC in the TCGA database. We calculated the stemness index of each patient using the one-class logistic regression (OCLR) algorithm and performed correlation analysis with immune infiltration. We used consensus clustering methods to classify OC patients into different stemness subtypes and compared the differences in immune infiltration between them. Finally, we established a prognostic signature by Cox and LASSO regression analysis. We found a significant negative correlation between a high stemness index and immune score. Pathway analysis indicated that the differentially expressed genes (DEGs) from the low- and high-mRNAsi groups were enriched in multiple functions and pathways, such as protein digestion and absorption, the PI3K-Akt signaling pathway, and the TGF-β signaling pathway. By consensus cluster analysis, patients with OC were split into two stemness subtypes, with subtype II having a better prognosis and higher immune infiltration. Furthermore, we identified 11 key genes to construct the prognostic signature for patients with OC. Among these genes, the expression levels of nine, including SFRP2, MFAP4, CCDC80, COL16A1, DUSP1, VSTM2L, TGFBI, PXDN, and GAS1, were increased in the high-risk group. The analysis of the KM and ROC curves indicated that this prognostic signature had a great survival prediction ability and could independently predict the prognosis for patients with OC. We established a stemness index-related risk prognostic module for OC, which has prognostic-independent capabilities and is expected to improve the diagnosis and treatment of patients with OC.

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Section: Discussionmentioning

confidence: 99%

“…Drug resistance and high rates of recurrence are the main causes of this poor prognosis [ 3 ]. Currently, surgical debulking and chemotherapy are still the main treatment modalities for OC [ 4 ]. Moreover, immunotherapy is also applied to OC treatment owing to its widespread application [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Value of the Stemness Index in Ovarian Cancer Prognosis

Yuan

Pang

et al. 2022

Genes

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“…Due to the patients’ non-specific presentation and the lack of effective diagnostic tools, more than 75% of EOC patients are diagnosed at advanced stages (stage III to IV) [ 23 ]. Moreover, despite improvements in medical therapies [ 24 ], particularly with the incorporation of drugs targeting homologous recombination deficiency, EOC survival rates remain low and novel therapeutic approaches are urgently needed [ 25 ]. In this study, we have reported a novel therapeutic approach to the treatment of HGSOC.…”

Section: Discussionmentioning

confidence: 99%

Comparing Intraperitoneal and Intravenous Personalized ErbB2CAR-T for the Treatment of Epithelial Ovarian Cancer

et al. 2022

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High-grade serous ovarian carcinoma (HGSOC) is the most common type of epithelial ovarian cancer. The majority of cases are diagnosed at advanced stages, when intraperitoneal (IP) spread has already occurred. Despite significant surgical and chemotherapeutic advances in HGSOC treatment over the past decades, survival rates with HGSOC have only modestly improved. Chimeric antigen receptor (CAR)-T cells enable T cells to directly bind to tumor-associated antigens in a major histocompatibility complex-independent manner, thereby inducing tumor rejection. While CAR-T cell therapy shows great promise in hematological malignancies, its use in solid tumors is limited. Therefore, innovative approaches are needed to increase the specificity of CAR-modified T cells against solid tumors. The aim of this study was to assess the efficacy and safety of intraperitoneal (IP) versus intravenous (IV) CAR-T cell therapy in the treatment of HGSOC. We constructed a CAR that targets the ErbB2/HER2 protein (ErbB2CAR), which is overexpressed in HGSOC, and evaluated the functionality of ErbB2CAR on ovarian cancer cell lines (OVCAR8, SKOV3, and NAR). Our findings show that an IP injection of ErbB2CAR-T cells to tumor-bearing mice led to disease remission and increased survival compared to the IV route. Moreover, we found that IP-injected ErbB2CART cells circulate to a lesser extent, making them safer for non-tumor tissues than IV-injected cells. Further supporting our findings, we show that the effect of ErbB2CAR-T cells on primary HGSOC tumors is correlated with ErbB2 expression. Together, these data demonstrate the advantages of an IP administration of CAR-T cells over IV administration, offering not only a safer strategy but also the potential for counteracting the effect of ErbB2CAR in HGSOC. Significance: IP-injected ErbB2CAR-T cells led to disease remission and increased survival compared to the IV route. These findings demonstrate the advantages of IP administration, offering a safe treatment strategy with the potential for counteracting the effect of ErbB2CAR in HGSOC.

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“…Autophagy-related 16-like 1 (ATG16L) is required for this innate process, but it does ensure that lipidation occurs on the appropriate cell wall. These actions cause the phagophore to enlarge and close, controlling the formation of the autophagosome [ 32 ]. The autophagosome’s two layers merge with lysosomes just before closing, permitting degradation of the inner membrane and intra-autophagosome transfer to begin [ 33 ].…”

Section: Molecular Pathway Of the Autophagy Processmentioning

confidence: 99%

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

et al. 2022

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Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy’s dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC.

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Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements

Cited by 38 publications

References 172 publications

The Value of the Stemness Index in Ovarian Cancer Prognosis

The Value of the Stemness Index in Ovarian Cancer Prognosis

Comparing Intraperitoneal and Intravenous Personalized ErbB2CAR-T for the Treatment of Epithelial Ovarian Cancer

Therapeutic Aspects and Molecular Targets of Autophagy to Control Pancreatic Cancer Management

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