Frontiers in Pathogenesis and Therapeutics of Cancer

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Mechanisms of Diseases".

Deadline for manuscript submissions: closed (10 January 2023) | Viewed by 20208

Special Issue Editors

1. Division of Cancer Research and Training, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA
2. David Geffen UCLA School of Medicine, Los Angeles, CA, USA
3. UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
Interests: breast cancer; diabetes; metabolic syndrome; drug discovery; targeted therapy
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Co-Guest Editor
Department of Surgery, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
Interests: oncology; breast cancer; endometrial carcinoma; stem cell; surgery; regenerative medicine; radiotherapy; chemotherapy

Special Issue Information

Dear Colleagues,

In cancer treatment, the ultimate goal is to offer accurate and personalized treatment according to the specific situation of patients. In recent years, an increasing number of new cancer treatment regimens have been developed. Radiotherapy, chemotherapy, and more potential new therapies are all formulated according to the individual situation of patients and specific targets of different cancer subtypes. This Special Issue of the Journal of Personalized Medicine aims to explore the latest innovative treatments for all kinds of cancers, such as breast cancer, leukemia, endometrial carcinoma, and so on. We are pleased to invite you to contribute studies using basic science, clinical, and population-based approaches, including, but not limited to radiotherapy, chemotherapy, immunotherapy, and cell therapy. In this Special Issue, original research articles and reviews are welcome. Our goal is to demonstrate the scientific advances in this field and pave the way toward personalized medicine for treating cancers.

I look forward to receiving your contributions.

Dr. Yong Wu
Dr. Jin Zhang
Guest Editors

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Keywords

  • radiation therapy
  • chemotherapy
  • cancer
  • precision medicine
  • personalized medicine
  • CART
  • immunotherapy
  • targeted therapy
  • cellular therapy
  • oncology

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Published Papers (7 papers)

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Editorial

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1 pages, 151 KiB  
Editorial
Advancing Cancer Research: Insights and Innovations in Pathogenesis and Targeted Therapies
by Yong Wu and Jaydutt V. Vadgama
J. Pers. Med. 2023, 13(3), 375; https://doi.org/10.3390/jpm13030375 - 21 Feb 2023
Viewed by 1301
Abstract
Cancer is a global health challenge that continues to affect millions of people, despite extensive research efforts [...] Full article
(This article belongs to the Special Issue Frontiers in Pathogenesis and Therapeutics of Cancer)

Research

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11 pages, 1722 KiB  
Article
The Efficacy of DW and T1-W MRI Combined with CT in the Preoperative Evaluation of Cholesteatoma
by Wan-Hsuan Sun, Jiun-Kai Fan and Tzu-Chin Huang
J. Pers. Med. 2022, 12(8), 1349; https://doi.org/10.3390/jpm12081349 - 21 Aug 2022
Cited by 4 | Viewed by 2932
Abstract
Objective: This study aims to assess the efficacy of diffusion-weighted (DW) and T1-weighted (T1W) magnetic resonance imaging (MRI) combined with high-resolution computed tomography (HRCT) (together as DW-T1W-CT) in the preoperative evaluation of the presence and extent of cholesteatoma, which helps determine whether a [...] Read more.
Objective: This study aims to assess the efficacy of diffusion-weighted (DW) and T1-weighted (T1W) magnetic resonance imaging (MRI) combined with high-resolution computed tomography (HRCT) (together as DW-T1W-CT) in the preoperative evaluation of the presence and extent of cholesteatoma, which helps determine whether a patient is suitable for transcanal endoscopic ear surgery (TEES). Methods: This retrospective study included 35 patients (18 male and 17 female) aged from 2 to 81 years diagnosed with chronic otitis media with or without cholesteatoma, who had received surgical treatment and a preoperative MRI and HRCT during the period of December 2015 to December 2020 at Cathay General Hospital. We compared the preoperative DW-T1W-CT findings with the intraoperative findings and final pathologic diagnosis. The accurate predictive value was evaluated using the presence of cholesteatoma and its extent. Results: Regarding the efficacy of detecting cholesteatoma, we found a sensitivity of 92% (23/25 cases with cholesteatoma), a specificity of 90% (9/10 cases without cholesteatoma), and an overall accurate predictive value of 91.4% (32/35) by using combined DW-T1W-CT imaging. With regard to evaluating the extent of cholesteatoma, the combined DW-T1W-CT images obtained an accurate predictive value of 84% (21/25 cases of cholesteatoma). Conclusion: Combined DW-T1W-CT has been proven to be a reliable tool in detecting the presence of cholesteatoma. It is also useful in preoperatively depicting the extent of cholesteatoma, which is crucial for determining whether a patient is suitable for TEES, aiding in surgical planning and patient consultation. Full article
(This article belongs to the Special Issue Frontiers in Pathogenesis and Therapeutics of Cancer)
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12 pages, 2818 KiB  
Article
Diaporine Potentiates the Anticancer Effects of Oxaliplatin and Doxorubicin on Liver Cancer Cells
by Shiliu Tian, Rui Su, Ke Wu, Xuhan Zhou, Jaydutt V. Vadgama and Yong Wu
J. Pers. Med. 2022, 12(8), 1318; https://doi.org/10.3390/jpm12081318 - 16 Aug 2022
Cited by 3 | Viewed by 2303
Abstract
Recent studies have shown that diaporine, a novel fungal metabolic product, has a strong in vitro and in vivo anticancer effect on human non-small-cell lung and breast cancers. In this study, three human hepatocarcinoma cell lines (HepG2, Hep3B, and Huh7) were used to [...] Read more.
Recent studies have shown that diaporine, a novel fungal metabolic product, has a strong in vitro and in vivo anticancer effect on human non-small-cell lung and breast cancers. In this study, three human hepatocarcinoma cell lines (HepG2, Hep3B, and Huh7) were used to evaluate the efficacy of diaporine alone and in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin for the treatment of liver cancer. We demonstrated that diaporine, oxaliplatin, and doxorubicin triggered a concentration- and time-dependent decrease in the number of HepG2 cells. Diaporine at a concentration of 2.5 μM showed almost 100% inhibition of cell counts at 72 h. Similar effects were observed only with much higher concentrations (100 μM) of oxaliplatin or doxorubicin. Decreases in cell numbers after 48 h treatment with diaporine, oxaliplatin, and doxorubicin were also demonstrated in two additional hepatoma cell lines, Hep3B and Huh7. The combination of these drugs at low concentration for 48 h in vitro noticeably showed that diaporine improved the inhibitory effect on the number of cancer cells induced by oxaliplatin or doxorubicin. Additionally, this combination effectively inhibited colony growth in vitro. We found that inhibition of phosphorylation of ERK1/2 significantly increased when diaporine was used in combination with other agents. In addition, we also found that when diaporine was used in combination with doxorubicin or oxaliplatin, their proapoptotic effect greatly increased. We further revealed that the induction of apoptosis in hepatoma cells after treatment is due, at least in part, to the inhibition of phosphorylation of AKT, leading to the activation of caspase-3, inactivation of poly (ADP-ribose) polymerase (PARP), and subsequently to DNA damage, as indicated by the increased level of H2AX. Based on these findings, we suggest that diaporine in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin may play a role in the treatment of liver cancer. Full article
(This article belongs to the Special Issue Frontiers in Pathogenesis and Therapeutics of Cancer)
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9 pages, 1442 KiB  
Article
Molecular Profile and Prognostic Value of BAP1 Mutations in Intrahepatic Cholangiocarcinoma: A Genomic Database Analysis
by Alessandro Rizzo, Riccardo Carloni, Angela Dalia Ricci, Alessandro Di Federico, Deniz Can Guven, Suayib Yalcin and Giovanni Brandi
J. Pers. Med. 2022, 12(8), 1247; https://doi.org/10.3390/jpm12081247 - 29 Jul 2022
Cited by 5 | Viewed by 2411
Abstract
Background. Recent years have witnessed the advent of molecular profiling for intrahepatic cholangiocarcinoma (iCCA), and new techniques have led to the identification of several molecular alterations. Precision oncology approaches have been widely evaluated and are currently under assessment, as shown by the recent [...] Read more.
Background. Recent years have witnessed the advent of molecular profiling for intrahepatic cholangiocarcinoma (iCCA), and new techniques have led to the identification of several molecular alterations. Precision oncology approaches have been widely evaluated and are currently under assessment, as shown by the recent development of a wide range of agents targeting Fibroblast Growth Factor Receptor (FGFR) 2, Isocitrate Dehydrogenase 1 (IDH-1), and BRAF. However, several knowledge gaps persist in the understanding of the genomic landscape of this hepatobiliary malignancy. Methods. In the current study, we aimed to comprehensively analyze clinicopathological features of BAP1-mutated iCCA patients in public datasets to increase the current knowledge on the molecular and biological profile of iCCA. Results. The current database study, including 772 iCCAs, identified BAP1 mutations in 120 cases (15.7%). According to our analysis, no differences in terms of overall survival and relapse-free survival were observed between BAP1-mutated and BAP1 wild-type patients receiving radical surgery. In addition, IDH1, PBRM1, and ARID1A mutations were the most commonly co-altered genes in BAP1-mutated iCCAs. Conclusions. The genomic characterization of iCCA is destined to become increasingly important, and more efforts aimed to implement iCCA genomics analysis are warranted. Full article
(This article belongs to the Special Issue Frontiers in Pathogenesis and Therapeutics of Cancer)
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18 pages, 7417 KiB  
Article
Comprehensive Analysis and Experimental Validation of a Novel Estrogen/Progesterone-Related Prognostic Signature for Endometrial Cancer
by Jing Yu, Hong-Wen Yao, Ting-Ting Liu, Di Wang, Jian-Hong Shi, Guang-Wen Yuan, Sai Ma and Ling-Ying Wu
J. Pers. Med. 2022, 12(6), 914; https://doi.org/10.3390/jpm12060914 - 31 May 2022
Cited by 3 | Viewed by 2563
Abstract
Estrogen and progesterone are the major determinants of the occurrence and development of endometrial cancer (EC), which is one of the most common gynecological cancers worldwide. Our purpose was to develop a novel estrogen/progesterone-related gene signature to better predict the prognosis of EC [...] Read more.
Estrogen and progesterone are the major determinants of the occurrence and development of endometrial cancer (EC), which is one of the most common gynecological cancers worldwide. Our purpose was to develop a novel estrogen/progesterone-related gene signature to better predict the prognosis of EC and help discover effective therapeutic strategies. We downloaded the clinical and RNA-seq data of 397 EC patients from The Cancer Genome Atlas (TCGA) database. The “limma” R package was used to screen for estrogen/progesterone-related differentially expressed genes (DEGs) between EC and normal tissues. Univariate and multivariate Cox proportional hazards regression analyses were applied to identify these DEGs that were associated with prognosis; then, a novel estrogen/progesterone-related prognostic signature comprising CDC25B, GNG3, ITIH3, PRXL2A and SDHB was established. The Kaplan–Meier (KM) survival analysis showed that the low-risk group identified by this signature had significantly longer overall survival (OS) than the high-risk group; the receiver operating characteristic (ROC) and risk distribution curves suggested this signature was an accurate predictor independent of risk factors. A nomogram incorporating the signature risk score and stage was constructed, and the calibration plot suggested it could accurately predict the survival rate. Compared with normal tissues, tumor tissues had increased mRNA levels of GNG3 and PRXL2A and a reduced mRNA level of ITIH3. The knockdown of PRXL2A and GNG3 significantly inhibited the proliferation and colony formation of Ishikawa and AN3CA cells, while the inhibition of PRXL2A expression suppressed xenograft growth. In this study, five estrogen/progesterone-related genes were identified and incorporated into a novel signature, which provided a new classification tool for improved risk assessment and potential molecular targets for EC therapies. Full article
(This article belongs to the Special Issue Frontiers in Pathogenesis and Therapeutics of Cancer)
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13 pages, 3869 KiB  
Article
Sensory Ion Channel Candidates Inform on the Clinical Course of Pancreatic Cancer and Present Potential Targets for Repurposing of FDA-Approved Agents
by Wenjie Shi, Chen Li, Thomas Wartmann, Christoph Kahlert, Renfei Du, Aristotelis Perrakis, Thomas Brunner, Roland S. Croner and Ulf D. Kahlert
J. Pers. Med. 2022, 12(3), 478; https://doi.org/10.3390/jpm12030478 - 16 Mar 2022
Cited by 23 | Viewed by 4534
Abstract
Background: Transient receptor potential channels (TRPs) have been demonstrated to take on functions in pancreatic adenocarcinoma (PAAD) biology. However, little data are available that validate the potential of TRP in a clinical translational setting. Methods: A TRPs-related gene signature was constructed based on [...] Read more.
Background: Transient receptor potential channels (TRPs) have been demonstrated to take on functions in pancreatic adenocarcinoma (PAAD) biology. However, little data are available that validate the potential of TRP in a clinical translational setting. Methods: A TRPs-related gene signature was constructed based on the Cox regression using a TCGA-PAAD cohort and receiver operating characteristic (ROC) was used to evaluate the predictive ability of this model. Core genes of the signature were screened by a protein-to-protein interaction (PPI) network, and expression validated by two independent datasets. The mutation analysis and gene set enrichment analysis (GSEA) were conducted. Virtual interventions screening was performed to discover substance candidates for the identified target genes. Results: A four TRPs-related gene signature, which contained MCOLN1, PKD1, TRPC3, and TRPC7, was developed and the area under the curve (AUC) was 0.758. Kaplan–Meier analysis revealed that patients with elevated signature score classify as a high-risk group featuring significantly shorter recurrence free survival (RFS) time, compared to the low-risk patients (p < 0.001). The gene prediction model also had a good predictive capability for predicting shortened overall survival (OS) and disease-specific survival (DSS) (AUC = 0.680 and AUC = 0.739, respectively). GSEA enrichment revealed the core genes of the signature, TRPC3 and TRPC7, were involved in several cancer-related pathways. TRPC3 mRNA is elevated in cancer tissue compared to control tissue and augmented in tumors with lymph node invasion compared to tumors without signs of lymph node invasion. Virtual substance screening of FDA approved compounds indicates that four small molecular compounds might be potentially selective not only for TRPC3 protein but also as a potential binding partner to TRPC7 protein. Conclusions: Our computational pipeline constructed a four TRP-related gene signature that enables us to predict clinical prognostic value of hitherto unrecognized biomarkers for PAAD. Sensory ion channels TRPC3 and TRPC7 could be the potential therapeutic targets in pancreatic cancer and TRPC3 might be involved in dysregulating mitochondrial functions during PAAD genesis. Full article
(This article belongs to the Special Issue Frontiers in Pathogenesis and Therapeutics of Cancer)
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Review

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16 pages, 1039 KiB  
Review
Immune Cells in Head-and-Neck Tumor Microenvironments
by Enar Jumaniyazova, Anastasiya Lokhonina, Dzhuliia Dzhalilova, Anna Kosyreva and Timur Fatkhudinov
J. Pers. Med. 2022, 12(9), 1521; https://doi.org/10.3390/jpm12091521 - 16 Sep 2022
Cited by 7 | Viewed by 2744
Abstract
Head-and-neck cancers constitute a heterogeneous group of aggressive tumors with high incidence and low survival rates, collectively being the sixth most prevalent cancer type globally. About 90% of head-and-neck cancers are classified as squamous cell carcinomas (HNSCC). The innate and adaptive immune systems, [...] Read more.
Head-and-neck cancers constitute a heterogeneous group of aggressive tumors with high incidence and low survival rates, collectively being the sixth most prevalent cancer type globally. About 90% of head-and-neck cancers are classified as squamous cell carcinomas (HNSCC). The innate and adaptive immune systems, indispensable for anti-cancer immune surveillance, largely define the rates of HNSCC emergence and progression. HNSCC microenvironments harbor multiple cell types that infiltrate the tumors and interact both with tumor cells and among themselves. Gradually, tumor cells learn to manipulate the immune system, either by adapting their own immunogenicity or through the release of immunosuppressive molecules. These interactions continuously evolve and shape the tumor microenvironment, both structurally and functionally, facilitating angiogenesis, proliferation and metastasis. Our understanding of this evolution is directly related to success in the development of advanced therapies. This review focuses on the key mechanisms that rule HNSCC infiltration, featuring particular immune cell types and their roles in the pathogenesis. A close focus on the tumor-immunity interactions will help identify new immunotherapeutic targets in patients with HNSCC. Full article
(This article belongs to the Special Issue Frontiers in Pathogenesis and Therapeutics of Cancer)
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