Research

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14 pages, 1192 KiB

Open AccessArticle

Expression of Soluble Form of Aurora A as a Predictive Factor for Neoadjuvant Therapy in Breast Cancer Patients: A Single-Center Pilot Study

by Pawel Winter, Malgorzata Fuksiewicz, Agnieszka Jagiello-Gruszfeld, Zbigniew Nowecki and Beata Kotowicz

Cancers 2023, 15(22), 5446; https://doi.org/10.3390/cancers15225446 - 16 Nov 2023

Cited by 1 | Viewed by 960

Abstract

Purpose: To search for new predictive breast cancer biomarkers. We analyzed the serum concentrations of biomarkers involved in carcinogenesis, which can also be targeted by therapy. Methods: In a single-center prospective study, the serum levels of Aurora A, thymidine kinase 1, and human [...] Read more.

Purpose: To search for new predictive breast cancer biomarkers. We analyzed the serum concentrations of biomarkers involved in carcinogenesis, which can also be targeted by therapy. Methods: In a single-center prospective study, the serum levels of Aurora A, thymidine kinase 1, and human epidermal growth factor receptor type 3 (HER3) were determined in 119 women with BC before neoadjuvant treatment using ELISA kits. Results: The following clinical data were analyzed: age; TNM; the expression of ER, PGR, HER2, and Ki67; histological grade (G); and the response to neoadjuvant treatment (NAT) in the residual tumor burden classification (RCB). A complete pathological response (pCR) was achieved after NAT in 41 patients (34%). The highest proportion of the patients with a confirmed pCR was found for triple negative breast cancer (TNBC) (62.5%); non-luminal HER2-positive (52.6%) cancer subtypes (p = 0.0003); and in the G3 group (50%; p = 0.0078). The patients with higher levels of Aurora A were more likely to achieve pCR (p = 0.039). In the multivariate analysis, the serum Aurora A levels ≥ 4.75 ng/mL correlated with a higher rate of pCR (OR: 3.5; 95% CI: 1.2–10.1; p = 0.023). Conclusions: We showed that in a biologically heterogeneous group of BC patients, the pretreatment serum Aurora A levels were of significant value in predicting the response to NAT. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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15 pages, 4737 KiB

Open AccessArticle

Integrated Analysis Identifies DPP7 as a Prognostic Biomarker in Colorectal Cancer

by Wei Zhang, Haidong Wang, Huadi Wang, Chuchu Xu, Rongjie Zhao, Junlin Yao, Chongya Zhai, Weidong Han, Hongming Pan and Jin Sheng

Cancers 2023, 15(15), 3954; https://doi.org/10.3390/cancers15153954 - 03 Aug 2023

Viewed by 1075

Abstract

Colorectal cancer has a poor prognosis and is prone to recurrence and metastasis. DPP7, a prolyl peptidase, is reported to regulate lymphocyte quiescence. However, the correlation of DPP7 with prognosis in CRC remains unclear. With publicly available cohorts, the Wilcoxon rank-sum test and [...] Read more.

Colorectal cancer has a poor prognosis and is prone to recurrence and metastasis. DPP7, a prolyl peptidase, is reported to regulate lymphocyte quiescence. However, the correlation of DPP7 with prognosis in CRC remains unclear. With publicly available cohorts, the Wilcoxon rank-sum test and logistic regression were employed to analyze the relationship between DPP7 expression and the clinicopathological features of CRC patients. Specific pathways of differentially expressed genes were determined through biofunctional analysis and gene set enrichment analysis (GSEA). qPCR and immunohistochemical staining were used to determine DPP7 expression levels in surgical specimens. The public dataset and analysis of the biospecimens of CRC patients revealed that DPP7, in the CRC samples, was expressed significantly higher than in non-tumor tissues. Moreover, increased DPP7 was significantly associated with a higher N stage, lymphatic invasion, and shorter overall survival. Functionally, DPP7 is involved in neuroactive ligand–receptor interaction and olfactory transduction signaling. We identified a series of targeted drugs and small-molecule drugs with responses to DPP7. To conclude, DPP7 is a valuable diagnostic and prognostic biomarker for CRC and considered as a new therapeutic target. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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19 pages, 3654 KiB

Open AccessArticle

Insights of Platinum Drug Interaction with Spinel Magnetic Nanocomposites for Targeted Anti-Cancer Effect

by Dana Almohazey, Vijaya Ravinayagam, Widyan Alamoudi, Sultan Akhtar, H. Dafalla, Hind Nasser AlSuwaidan, Shoruq. T. Almutairi, Hajer Saleh Alghamdi, Sukaina Ahmed Aldamen, M. A. Almessiere, A. Baykal, Ahmed A. Maarouf and B. Rabindran Jermy

Cancers 2023, 15(3), 695; https://doi.org/10.3390/cancers15030695 - 23 Jan 2023

Cited by 2 | Viewed by 2098

Abstract

In nanotherapeutics, gaining insight about the drug interaction with the pore architecture and surface functional groups of nanocarriers is crucial to aid in the development of targeted drug delivery. Manganese ferrite impregnated graphene oxide (MnFe₂O₄/GO) with a two-dimensional sheet [...] Read more.

In nanotherapeutics, gaining insight about the drug interaction with the pore architecture and surface functional groups of nanocarriers is crucial to aid in the development of targeted drug delivery. Manganese ferrite impregnated graphene oxide (MnFe₂O₄/GO) with a two-dimensional sheet and spherical silica with a three-dimensional interconnected porous structure (MnFe₂O₄/silica) were evaluated for cisplatin release and cytotoxic effects. Characterization studies revealed the presence of Mn²⁺ species with a variable spinel cubic phase and superparamagnetic effect. We used first principles calculations to study the physisorption of cisplatin on monodispersed silica and on single- and multi-layered GO. The binding energy of cisplatin on silica and single-layer GO was ~1.5 eV, while it was about double that value for the multilayer GO structure. Moreover, we treated MCF-7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) with our nanocomposites and used the cell viability assay MTT. Both nanocomposites significantly reduced the cell viability. Pt⁴⁺ species of cisplatin on the spinel ferrite/silica nanocomposite had a better effect on the cytotoxic capability when compared to GO. The EC50 for MnFe₂O₄/silica/cisplatin and MnFe₂O₄/GO/cisplatin on MCF-7 was: 48.43 µg/mL and 85.36 µg/mL, respectively. The EC50 for the same conditions on HFF was: 102.92 µg/mL and 102.21 µg/mL, respectively. In addition, immunofluorescence images using c-caspase 3/7, and TEM analysis indicated that treating cells with these nanocomposites resulted in apoptosis as the major mechanism of cell death. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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13 pages, 3156 KiB

Open AccessArticle

CircKIF4A Is a Prognostic Factor and Modulator of Natural Killer/T-Cell Lymphoma Progression

by Rongfang He, Wei Wen, Bibo Fu, Renjie Zhu, Guanjun Chen, Shenrui Bai, Xi Cao and Hua Wang

Cancers 2022, 14(19), 4950; https://doi.org/10.3390/cancers14194950 - 09 Oct 2022

Cited by 2 | Viewed by 1720

Abstract

Background: Natural killer/T-cell lymphoma (NKTL) is difficult to treat. Circular RNAs (circ RNAs) have been implicated in tumorigenesis. However, the function of circKIF4A in NKTL has not been investigated. Methods: QPCR analysis was used to compare circKIF4A levels in NKTL cell lines versus [...] Read more.

Background: Natural killer/T-cell lymphoma (NKTL) is difficult to treat. Circular RNAs (circ RNAs) have been implicated in tumorigenesis. However, the function of circKIF4A in NKTL has not been investigated. Methods: QPCR analysis was used to compare circKIF4A levels in NKTL cell lines versus normal cell lines. Kaplan–Meier survival analysis was used to assess the effect of circKIF4A on the prognosis of NKTL. The correlation between clinicopathological features and circKIF4A expression was examined using cox regression analysis. Luciferase reporter, RNA immunoprecipitation and immunohistochemistry assays were also used to investigate the mechanisms of circKIF4A in NKTL. Results: Our analyses revealed that circKIF4A is significantly upregulated in NKTL cell lines and that its upregulation correlates with the poor prognosis of NKTL. The silencing of circKIF4A significantly suppressed glucose uptake and lactate production in NKTL cells. Moreover, we showed that circKIF4A, PDK1, and BCL11A bind miR-1231 and that circKIF4A regulates PDK1 and BCL11A expressions by sponging miR-1231. Conclusions: During NKTL progression, circKIF4A regulated PDK1 and BCL11A levels by sponging miR-1231. Our data indicated that circKIF4A is oncogenic in NKTL and that it is a predictor of poor prognosis of NKTL. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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10 pages, 1281 KiB

Open AccessCommunication

Efficacy and Safety of Amrubicin in Small Cell Carcinoma Previously Treated with Immune Checkpoint Inhibitors and Chemotherapy

by Tadashi Nishimura, Hajime Fujimoto, Takumi Fujiwara, Kentaro Ito, Atsushi Fujiwara, Hisamichi Yuda, Hidetoshi Itani, Masahiro Naito, Shuji Kodama, Akihiko Yagi, Valeria Fridman D’Alessandro, Taro Yasuma, Kazuki Furuhashi, Haruko Saiki, Tomohito Okano, Atsushi Tomaru, Motoaki Tanigawa, Corina N. D’Alessandro-Gabazza, Esteban C. Gabazza, Masamichi Yoshida, Osamu Hataji, Hidenori Ibata and Tetsu Kobayashi Show full author list Hide full author list

Cancers 2022, 14(16), 3953; https://doi.org/10.3390/cancers14163953 - 16 Aug 2022

Cited by 2 | Viewed by 2083

Abstract

Adding an immune checkpoint inhibitor to chemotherapy to treat extensive-stage small cell lung cancer is effective. However, there are no reports of an effective second-line treatment in patients previously treated with chemotherapy and immune checkpoint inhibitors as a first-line treatment. Here, we assessed [...] Read more.

Adding an immune checkpoint inhibitor to chemotherapy to treat extensive-stage small cell lung cancer is effective. However, there are no reports of an effective second-line treatment in patients previously treated with chemotherapy and immune checkpoint inhibitors as a first-line treatment. Here, we assessed the efficacy and safety of amrubicin as a second-line treatment for extensive-stage small cell lung cancer after chemotherapy and immune checkpoint inhibitor combination therapy. The study enrolled 150 patients with extensive-stage small cell lung cancer. The efficacy and the incidence of adverse events were compared between patients previously treated with immune checkpoint inhibitors and patients without previous immune checkpoint inhibitor treatment. One hundred and twenty-three patients were eligible. There was no difference in objective response rate, time-to-treatment failure, progression-free survival, and overall survival between both groups. The incidence of adverse events was similar in both treatment groups. Pretreatment with immune checkpoint inhibitors was not associated with an increase in amrubicin-related adverse events. This study shows that the efficacy of amrubicin in extensive-stage small cell lung cancer remains unchanged irrespective of previous treatment with immune checkpoint inhibitors. Amrubicin-related adverse events did not increase in patients previously treated with immune checkpoint inhibitors. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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Review

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16 pages, 806 KiB

Open AccessReview

Multidisciplinary Team Care in Pituitary Tumours

by Pedro Marques, Amets Sagarribay, Francisco Tortosa, Lia Neto, Joana Tavares Ferreira, João Subtil, Ana Palha, Daniela Dias and Inês Sapinho

Cancers 2024, 16(5), 950; https://doi.org/10.3390/cancers16050950 - 27 Feb 2024

Viewed by 613

Abstract

The optimal care for patients with pituitary tumours is best provided in a multidisciplinary and collaborative environment, which requires the contribution of multiple medical specialties working together. The benefits and advantages of the pituitary multidisciplinary team (MDT) are broad, and all relevant international [...] Read more.

The optimal care for patients with pituitary tumours is best provided in a multidisciplinary and collaborative environment, which requires the contribution of multiple medical specialties working together. The benefits and advantages of the pituitary multidisciplinary team (MDT) are broad, and all relevant international consensus and guidelines in the field recommend that patients with pituitary tumours should always be managed in a MDT. Endocrinologists and neurosurgeons are normally the leading specialties within the pituitary MDT, supported by many other specialties with significant contributions to the diagnosis and management of pituitary tumours, including neuropathology, neuroradiology, neuro-ophthalmology, and otorhinolaryngology, among others. Here, we review the literature concerning the concepts of Pituitary MDT/Pituitary Tumour Centre of Excellence (PTCOE) in terms of their mission, goals, benefits, structure, proposed models of function, and barriers, and we also provide the views of different specialists involved in our Pituitary MDT. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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23 pages, 1962 KiB

Open AccessReview

Addressing Genetic Tumor Heterogeneity, Post-Therapy Metastatic Spread, Cancer Repopulation, and Development of Acquired Tumor Cell Resistance

by Dennis Christoph Harrer, Florian Lüke, Tobias Pukrop, Lina Ghibelli, Albrecht Reichle and Daniel Heudobler

Cancers 2024, 16(1), 180; https://doi.org/10.3390/cancers16010180 - 29 Dec 2023

Cited by 2 | Viewed by 1288

Abstract

The concept of post-therapy metastatic spread, cancer repopulation and acquired tumor cell resistance (M-CRAC) rationalizes tumor progression because of tumor cell heterogeneity arising from post-therapy genetic damage and subsequent tissue repair mechanisms. Therapeutic strategies designed to specifically address M-CRAC involve tissue editing approaches, [...] Read more.

The concept of post-therapy metastatic spread, cancer repopulation and acquired tumor cell resistance (M-CRAC) rationalizes tumor progression because of tumor cell heterogeneity arising from post-therapy genetic damage and subsequent tissue repair mechanisms. Therapeutic strategies designed to specifically address M-CRAC involve tissue editing approaches, such as low-dose metronomic chemotherapy and the use of transcriptional modulators with or without targeted therapies. Notably, tumor tissue editing holds the potential to treat patients, who are refractory to or relapsing (r/r) after conventional chemotherapy, which is usually based on administering a maximum tolerable dose of a cytostatic drugs. Clinical trials enrolling patients with r/r malignancies, e.g., non-small cell lung cancer, Hodgkin’s lymphoma, Langerhans cell histiocytosis and acute myelocytic leukemia, indicate that tissue editing approaches could yield tangible clinical benefit. In contrast to conventional chemotherapy or state-of-the-art precision medicine, tissue editing employs a multi-pronged approach targeting important drivers of M-CRAC across various tumor entities, thereby, simultaneously engaging tumor cell differentiation, immunomodulation, and inflammation control. In this review, we highlight the M-CRAC concept as a major factor in resistance to conventional cancer therapies and discusses tissue editing as a potential treatment. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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23 pages, 1293 KiB

Open AccessReview

Multilevel Heterogeneity of Colorectal Cancer Liver Metastasis

by Hao Chen, Chongya Zhai, Xian Xu, Haidong Wang, Weidong Han and Jiaying Shen

Cancers 2024, 16(1), 59; https://doi.org/10.3390/cancers16010059 - 21 Dec 2023

Viewed by 963

Abstract

Colorectal cancer liver metastasis (CRLM) is a highly heterogeneous disease. Therapies that target both primary foci and liver metastasis are severely lacking. Therefore, understanding the features of metastatic tumor cells in the liver is valuable for the overall control of CRLM patients. In [...] Read more.

Colorectal cancer liver metastasis (CRLM) is a highly heterogeneous disease. Therapies that target both primary foci and liver metastasis are severely lacking. Therefore, understanding the features of metastatic tumor cells in the liver is valuable for the overall control of CRLM patients. In this review, we summarize the heterogeneity exhibited in CRLM from five aspects (gene, transcriptome, protein, metabolism, and immunity). In addition to genetic heterogeneity, the other four aspects exhibit significant heterogeneity. Compared to primary CRC, the dysregulation of epithelial–mesenchymal transition (EMT)-related proteins, the enhanced metabolic activity, and the increased infiltration of immunosuppressive cells are detected in CRLM. Preclinical evidence shows that targeting the EMT process or enhancing cellular metabolism may represent a novel approach to increasing the therapeutic efficacy of CRLM. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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23 pages, 1891 KiB

Open AccessReview

Small Antibodies with Big Applications: Nanobody-Based Cancer Diagnostics and Therapeutics

by Qian Zhang, Nan Zhang, Han Xiao, Chen Wang and Lian He

Cancers 2023, 15(23), 5639; https://doi.org/10.3390/cancers15235639 - 29 Nov 2023

Cited by 1 | Viewed by 1930

Abstract

Monoclonal antibodies (mAbs) have exhibited substantial potential as targeted therapeutics in cancer treatment due to their precise antigen-binding specificity. Despite their success in tumor-targeted therapies, their effectiveness is hindered by their large size and limited tissue permeability. Camelid-derived single-domain antibodies, also known as [...] Read more.

Monoclonal antibodies (mAbs) have exhibited substantial potential as targeted therapeutics in cancer treatment due to their precise antigen-binding specificity. Despite their success in tumor-targeted therapies, their effectiveness is hindered by their large size and limited tissue permeability. Camelid-derived single-domain antibodies, also known as nanobodies, represent the smallest naturally occurring antibody fragments. Nanobodies offer distinct advantages over traditional mAbs, including their smaller size, high stability, lower manufacturing costs, and deeper tissue penetration capabilities. They have demonstrated significant roles as both diagnostic and therapeutic tools in cancer research and are also considered as the next generation of antibody drugs. In this review, our objective is to provide readers with insights into the development and various applications of nanobodies in the field of cancer treatment, along with an exploration of the challenges and strategies for their prospective clinical trials. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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19 pages, 2891 KiB

Open AccessReview

Advancements and Obstacles of PARP Inhibitors in Gastric Cancer

by Hongjie Chen, Yangchan Hu, Zirui Zhuang, Dingyi Wang, Zu Ye, Ji Jing and Xiangdong Cheng

Cancers 2023, 15(21), 5114; https://doi.org/10.3390/cancers15215114 - 24 Oct 2023

Viewed by 1174

Abstract

Gastric cancer (GC) is a common and aggressive cancer of the digestive system, exhibiting high aggressiveness and significant heterogeneity. Despite advancements in improving survival rates over the past few decades, GC continues to carry a worrisome prognosis and notable mortality. As a result, [...] Read more.

Gastric cancer (GC) is a common and aggressive cancer of the digestive system, exhibiting high aggressiveness and significant heterogeneity. Despite advancements in improving survival rates over the past few decades, GC continues to carry a worrisome prognosis and notable mortality. As a result, there is an urgent need for novel therapeutic approaches to address GC. Recent targeted sequencing studies have revealed frequent mutations in DNA damage repair (DDR) pathway genes in many GC patients. These mutations lead to an increased reliance on poly (adenosine diphosphate-ribose) polymerase (PARP) for DNA repair, making PARP inhibitors (PARPi) a promising treatment option for GC. This article presents a comprehensive overview of the rationale and development of PARPi, highlighting its progress and challenges in both preclinical and clinical research for treating GC. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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16 pages, 2512 KiB

Open AccessReview

The Role of GAB1 in Cancer

by Manuel Jesús Pérez-Baena, Francisco Josué Cordero-Pérez, Jesús Pérez-Losada and Marina Holgado-Madruga

Cancers 2023, 15(16), 4179; https://doi.org/10.3390/cancers15164179 - 20 Aug 2023

Viewed by 1677

Abstract

GRB2-associated binder 1 (GAB1) is the inaugural member of the GAB/DOS family of pleckstrin homology (PH) domain-containing proteins. Upon receiving various stimuli, GAB1 transitions from the cytoplasm to the membrane where it is phosphorylated by a range of kinases. This event recruits SH2 [...] Read more.

GRB2-associated binder 1 (GAB1) is the inaugural member of the GAB/DOS family of pleckstrin homology (PH) domain-containing proteins. Upon receiving various stimuli, GAB1 transitions from the cytoplasm to the membrane where it is phosphorylated by a range of kinases. This event recruits SH2 domain-containing proteins like SHP2, PI3K’s p85 subunit, CRK, and others, thereby activating distinct signaling pathways, including MAPK, PI3K/AKT, and JNK. GAB1-deficient embryos succumb in utero, presenting with developmental abnormalities in the heart, placenta, liver, skin, limb, and diaphragm myocytes. Oncogenic mutations have been identified in the context of cancer. GAB1 expression levels are disrupted in various tumors, and elevated levels in patients often portend a worse prognosis in multiple cancer types. This review focuses on GAB1’s influence on cellular transformation particularly in proliferation, evasion of apoptosis, metastasis, and angiogenesis—each of these processes being a cancer hallmark. GAB1 also modulates the resistance/sensitivity to antitumor therapies, making it a promising target for future anticancer strategies. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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15 pages, 1820 KiB

Open AccessReview

Parathyroid Hormone-Related Protein/Parathyroid Hormone Receptor 1 Signaling in Cancer and Metastasis

by Yawei Zhao, Shang Su and Xiaohong Li

Cancers 2023, 15(7), 1982; https://doi.org/10.3390/cancers15071982 - 26 Mar 2023

Cited by 4 | Viewed by 2551

Abstract

PTHrP exerts its effects by binding to its receptor, PTH1R, a G protein-coupled receptor (GPCR), activating the downstream cAMP signaling pathway. As an autocrine, paracrine, or intracrine factor, PTHrP has been found to stimulate cancer cell proliferation, inhibit apoptosis, and promote tumor-induced osteolysis [...] Read more.

PTHrP exerts its effects by binding to its receptor, PTH1R, a G protein-coupled receptor (GPCR), activating the downstream cAMP signaling pathway. As an autocrine, paracrine, or intracrine factor, PTHrP has been found to stimulate cancer cell proliferation, inhibit apoptosis, and promote tumor-induced osteolysis of bone. Despite these findings, attempts to develop PTHrP and PTH1R as drug targets have not produced successful results in the clinic. Nevertheless, the efficacy of blocking PTHrP and PTH1R has been shown in various types of cancer, suggesting its potential for therapeutic applications. In light of these conflicting data, we conducted a comprehensive review of the studies of PTHrP/PTH1R in cancer progression and metastasis and highlighted the strengths and limitations of targeting PTHrP or PTH1R in cancer therapy. This review also offers our perspectives for future research in this field. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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19 pages, 1437 KiB

Open AccessReview

Targeting TET2 as a Therapeutic Approach for Angioimmunoblastic T Cell Lymphoma

by Lina Hu, Xuanye Zhang, Huifeng Li, Suxia Lin and Shengbing Zang

Cancers 2022, 14(22), 5699; https://doi.org/10.3390/cancers14225699 - 20 Nov 2022

Cited by 2 | Viewed by 2865

Abstract

Angioimmunoblastic T-cell lymphoma (AITL), a type of malignant lymphoma with unique genomic aberrations, significant clinicopathological features, and poor prognosis, is characterized by immune system dysregulation. Recent sequencing studies have identified recurrent mutations and interactions in tet methylcytosine dioxygenase 2 (TET2), ras [...] Read more.

Angioimmunoblastic T-cell lymphoma (AITL), a type of malignant lymphoma with unique genomic aberrations, significant clinicopathological features, and poor prognosis, is characterized by immune system dysregulation. Recent sequencing studies have identified recurrent mutations and interactions in tet methylcytosine dioxygenase 2 (TET2), ras homology family member A (RHOA), DNA methyltransferase 3 alpha (DNMT3A), and mitochondrial isocitrate dehydrogenase II (IDH2). Notably, since B-cell lymphomas are frequently observed along with AITL, this review first summarizes its controversial mechanisms based on traditional and recent views. Epigenetic regulation represented by TET2 plays an increasingly important role in understanding the multi-step and multi-lineage tumorigenesis of AITL, providing new research directions and treatment strategies for patients with AITL. Here, we review the latest advances in our understanding of AITL and highlight relevant issues that have yet to be addressed in clinical practice. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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32 pages, 2600 KiB

Open AccessReview

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

by Yi Zhang, Qiong Li, Zhao Huang, Bowen Li, Edouard C. Nice, Canhua Huang, Liuya Wei and Bingwen Zou

Cancers 2022, 14(19), 4568; https://doi.org/10.3390/cancers14194568 - 21 Sep 2022

Cited by 28 | Viewed by 33832

Abstract

Reprogramming of glucose metabolism provides sufficient energy and raw materials for the proliferation, metastasis, and immune escape of cancer cells, which is enabled by glucose metabolism-related enzymes that are abundantly expressed in a broad range of cancers. Therefore, targeting glucose metabolism enzymes has [...] Read more.

Reprogramming of glucose metabolism provides sufficient energy and raw materials for the proliferation, metastasis, and immune escape of cancer cells, which is enabled by glucose metabolism-related enzymes that are abundantly expressed in a broad range of cancers. Therefore, targeting glucose metabolism enzymes has emerged as a promising strategy for anticancer drug development. Although several glucose metabolism modulators have been approved for cancer treatment in recent years, some limitations exist, such as a short half-life, poor solubility, and numerous adverse effects. With the rapid development of medicinal chemicals, more advanced and effective glucose metabolism enzyme-targeted anticancer drugs have been developed. Additionally, several studies have found that some natural products can suppress cancer progression by regulating glucose metabolism enzymes. In this review, we summarize the mechanisms underlying the reprogramming of glucose metabolism and present enzymes that could serve as therapeutic targets. In addition, we systematically review the existing drugs targeting glucose metabolism enzymes, including small-molecule modulators and natural products. Finally, the opportunities and challenges for glucose metabolism enzyme-targeted anticancer drugs are also discussed. In conclusion, combining glucose metabolism modulators with conventional anticancer drugs may be a promising cancer treatment strategy. Full article

(This article belongs to the Special Issue Advances in Cancer Therapeutics)

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