New Biomarkers in Cancers 2nd Edition

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: 15 December 2025 | Viewed by 20515

Special Issue Editor


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Guest Editor
1. Skin Cancer Unit, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany
2. Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany
Interests: skin cancer; malignant melanoma; translational research; stem cells
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Special Issue Information

Dear Colleagues,

This collection is the second edition of the previous one "New Biomarkers in Cancers" (https://www.mdpi.com/journal/cancers/special_issues/NBCancers).

In recent years, several new therapies have been approved for different cancer entities. Due to these new therapeutic options, physicians are confronted with new challenges, such as monitoring progression and stratifying patients for appropriate treatments.

Novel analytical techniques using body fluids, such as blood, and tumor tissue have identified numerous possible biomarkers.

In this Special Issue, we will publish reviews and original research that provide new insights into the role of predictive and prognostic tumor biomarkers. Novel insights into tumor biomarkers are particularly welcome.

Prof. Dr. Jochen Sven Utikal
Guest Editor

Manuscript Submission Information

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Keywords

  • cancer
  • biomarker
  • molecule
  • serum
  • tumor
  • liquid biopsy
  • circulating tumor DNA
  • DNA
  • RNA
  • protein
  • circulating tumor cells
  • prognosis
  • prediction
  • indicator
  • traceable substance

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Published Papers (10 papers)

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Research

Jump to: Review

14 pages, 460 KiB  
Article
Prevalence of Homologous Recombination Repair Mutations and Association with Clinical Outcomes in Patients with Solid Tumors: A Study Using the AACR Project GENIE Dataset
by Changxia Shao, Heng Zhou, Cai Chen, Elisha J. Dettman, Yixin Ren, Razvan Cristescu, Alexander Gozman and Fan Jin
Cancers 2025, 17(4), 577; https://doi.org/10.3390/cancers17040577 - 8 Feb 2025
Viewed by 809
Abstract
Background/Objectives: Mutations in BRCA1 and/or BRCA2 (BRCAm) and other homologous recombination repair genes (HRRm) are associated with several cancers. We evaluated the prevalence and association with overall survival (OS) of somatic BRCAm and HRRm among patients with advanced solid tumors. Methods: We used [...] Read more.
Background/Objectives: Mutations in BRCA1 and/or BRCA2 (BRCAm) and other homologous recombination repair genes (HRRm) are associated with several cancers. We evaluated the prevalence and association with overall survival (OS) of somatic BRCAm and HRRm among patients with advanced solid tumors. Methods: We used deidentified data from the AACR GENIE Biopharma Collaborative dataset derived from patients with tumors genotyped using next-generation sequencing between 1 January 2014 and 31 December 2017. Eligible patients were aged ≥18 years diagnosed with non-small-cell lung, colorectal, breast, bladder, prostate, or pancreatic cancer, with documented BRCA/HRR somatic mutation status. The primary analysis was OS (censored at the start of poly[ADP ribose] polymerase inhibitors [PARPi]/immunotherapy) after initiation of second-line therapy since most patients had sequencing after first-line therapy. Results: Among eligible patients, 242/7022 (3.4%) had BRCAm and 477/5474 (8.7%) had HRRm. Adjusted OS HRs (95% CI) for the primary analysis (using the initiation of second-line therapy as index date) were 0.79 (0.61–1.03) with/without BRCAm (n = 116/n = 3394) and 0.83 (0.69–0.99) with/without HRRm (n = 247/n = 2656); in sensitivity analysis of patients with stage IV disease, HRs were 0.97 (0.68–1.38) with/without BRCAm (n = 58/n = 1847) and 0.92 (0.73–1.18) with/without HRRm (n = 132/n = 1488). Conclusions: Overall, BRCAm and HRRm did not show a strong association with OS, with a trend toward longer OS among patients receiving standard second-line therapies excluding PARPi/immunotherapy. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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16 pages, 2388 KiB  
Article
Untargeted Metabolomics and Liquid Biopsy Investigation of Circulating Biomarkers in Soft Tissue Sarcoma
by Daniela Grasso, Barbara Marzocchi, Guido Scoccianti, Ilaria Palchetti, Domenico Andrea Campanacci, Lorenzo Antonuzzo, Federico Scolari, Serena Pillozzi and Andrea Bernini
Cancers 2025, 17(3), 553; https://doi.org/10.3390/cancers17030553 - 6 Feb 2025
Viewed by 788
Abstract
Background: Soft tissue sarcomas (STSs) are rare, highly malignant mesenchymal tumours, comprising approximately 1% of all adult cancers and about 15% of paediatric solid tumours. STSs exhibit considerable genomic complexity with diverse subtypes, posing significant clinical challenges. Objectives: This study aims to characterise [...] Read more.
Background: Soft tissue sarcomas (STSs) are rare, highly malignant mesenchymal tumours, comprising approximately 1% of all adult cancers and about 15% of paediatric solid tumours. STSs exhibit considerable genomic complexity with diverse subtypes, posing significant clinical challenges. Objectives: This study aims to characterise the molecular signature of primary STS through liquid biopsies and the untargeted metabolomic profiling of 75 patients, providing deep insights into cellular processes and potential therapeutic targets. Methods: This study analysed serum samples using nuclear magnetic resonance (NMR) spectroscopy for metabolomic profiling. Multivariate data analysis and machine learning classifiers were employed to identify biomarkers. Results: A panel of eleven significant deregulated metabolites were discovered in serum samples of patients with STS, with potential implications for cancer diagnosis and treatment. Conclusions: Choline decrease emerged as a marker for cancer progression, highlighting the potential of targeting its metabolism for therapeutic approaches in STS. The NMR analysis protocol proved effective for determining circulating biomarkers from liquid biopsies, making it suitable for rare disease research. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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19 pages, 1624 KiB  
Article
A New Blood-Based Epigenetic Diagnostic Biomarker Test (EpiSwitch®® NST) with High Sensitivity and Positive Predictive Value for Colorectal Cancer and Precancerous Polyps
by Ewan Hunter, Heba Alshaker, Cicely Weston, Mutaz Issa, Shekinah Bautista, Abel Gebregzabhar, Anya Virdi, Ann Dring, Ryan Powell, Jayne Green, Roshan Lal, Vamsi Velchuru, Kamal Aryal, Muhammad Radzi Bin Abu Hassan, Goh Tiong Meng, Janisha Suriakant Patel, Shameera Pharveen Mohamed Gani, Chun Ren Lim, Thomas Guiel, Alexandre Akoulitchev and Dmitri Pchejetskiadd Show full author list remove Hide full author list
Cancers 2025, 17(3), 521; https://doi.org/10.3390/cancers17030521 - 4 Feb 2025
Viewed by 1647
Abstract
Background/Objectives: Colorectal cancer (CRC) arises from the epithelial lining of the colon or rectum, often following a progression from benign adenomatous polyps to malignant carcinoma. Screening modalities such as colonoscopy, faecal immunochemical tests (FIT), and FIT-DNA are critical for early detection and prevention, [...] Read more.
Background/Objectives: Colorectal cancer (CRC) arises from the epithelial lining of the colon or rectum, often following a progression from benign adenomatous polyps to malignant carcinoma. Screening modalities such as colonoscopy, faecal immunochemical tests (FIT), and FIT-DNA are critical for early detection and prevention, but non-invasive methods lack sensitivity to polyps and early CRC. Chromosome conformations (CCs) are potent epigenetic regulators of gene expression. We have previously developed an epigenetic assay, EpiSwitch®®, that employs an algorithmic-based CCs analysis. Using EpiSwitch®® technology, we have shown the presence of cancer-specific CCs in peripheral blood mononuclear cells (PBMCs) and primary tumours of patients with melanoma and prostate cancer. EpiSwitch®®-based commercial tests are now available to diagnose prostate cancer with 94% accuracy (PSE test) and response to immune checkpoint inhibitors across 14 cancers with 85% accuracy (CiRT test). Methods/Results/Conclusions: Using blood samples collected from n = 171 patients with CRC, n = 44 patients with colorectal polyps and n = 110 patients with a ‘clear’ colonoscopy we performed whole Genome DNA screening for CCs correlating to CRC diagnosis. Our findings suggest the presence of two eight-marker CC signatures (EpiSwitch®® NST) in whole blood that allow diagnosis of CRC and precancerous polyps, respectively. Independent validation cohort testing demonstrated high accuracy in identifying colorectal polyps and early versus late stages of CRC with an exceptionally high sensitivity of 79–90% and a high positive prediction value of 60–84%. Linking the top diagnostic CCs to nearby genes, we have built pathways maps that likely underline processes contributing to the pathology of polyp and CRC progression, including TGFβ, cMYC, Rho GTPase, ROS, TNFa/NFκB, and APC. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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11 pages, 1061 KiB  
Article
Type IX Collagen Turnover Is Altered in Patients with Solid Tumors
by Helena Port, Yi He, Morten A. Karsdal, Emilie A. Madsen, Anne-Christine Bay-Jensen, Nicholas Willumsen and Signe Holm Nielsen
Cancers 2024, 16(11), 2035; https://doi.org/10.3390/cancers16112035 - 27 May 2024
Cited by 2 | Viewed by 1382
Abstract
The fibrotic tumor microenvironment, characterized by its intricate extracellular matrix (ECM), consists of many collagens with diverse functions and unexplored biomarker potential. Type IX collagen is a member of the low-abundance collagen family known as the fibril-associated collagen with interrupted triple helices (FACITs) [...] Read more.
The fibrotic tumor microenvironment, characterized by its intricate extracellular matrix (ECM), consists of many collagens with diverse functions and unexplored biomarker potential. Type IX collagen is a member of the low-abundance collagen family known as the fibril-associated collagen with interrupted triple helices (FACITs) and is found mostly in cartilage. Its role in the tumor microenvironment remains unexplored. To investigate the biomarker potential of a type IX collagen in cancer, an immuno-assay was developed (PRO-C9) and technical assay performance was evaluated for the assessment of serum. PRO-C9 levels were measured in serum samples from 259 patients with various solid tumor types compared to serum levels from 73 healthy controls. PRO-C9 levels were significantly elevated in patients with solid tumors including bladder, breast, colorectal, gastric, head and neck, lung, melanoma, ovarian, pancreatic, and renal compared to levels in healthy controls (p < 0.05–p < 0.0001). PRO-C9 could discriminate between patients with cancer and healthy controls, with the area under the receiver operating characteristic values ranging from 0.58 to 0.86 (p < 0.3–p < 0.0001), indicating potential diagnostic utility. This study suggests that type IX collagen turnover is altered in patients with solid tumors and demonstrates the feasibility of using PRO-C9 as a non-invasive serum-based biomarker with relevance in multiple cancer types. Furthermore, these results underscore the potential utility of PRO-C9 to better elucidate the biology of FACITs in cancers. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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16 pages, 3216 KiB  
Article
Protein Arginine Methylation Patterns in Plasma Small Extracellular Vesicles Are Altered in Patients with Early-Stage Pancreatic Ductal Adenocarcinoma
by Kritisha Bhandari, Jeng Shi Kong, Katherine Morris, Chao Xu and Wei-Qun Ding
Cancers 2024, 16(3), 654; https://doi.org/10.3390/cancers16030654 - 3 Feb 2024
Cited by 3 | Viewed by 2022
Abstract
Small extracellular vesicles (sEVs) contain lipids, proteins and nucleic acids, which often resemble their cells of origin. Therefore, plasma sEVs are considered valuable resources for cancer biomarker development. However, previous efforts have been largely focused on the level of proteins and miRNAs in [...] Read more.
Small extracellular vesicles (sEVs) contain lipids, proteins and nucleic acids, which often resemble their cells of origin. Therefore, plasma sEVs are considered valuable resources for cancer biomarker development. However, previous efforts have been largely focused on the level of proteins and miRNAs in plasma sEVs, and the post-translational modifications of sEV proteins, such as arginine methylation, have not been explored. Protein arginine methylation, a relatively stable post-translational modification, is a newly described molecular feature of PDAC. The present study examined arginine methylation patterns in plasma sEVs derived from patients with early-stage PDAC (n = 23) and matched controls. By utilizing the arginine methylation-specific antibodies for western blotting, we found that protein arginine methylation patterns in plasma sEVs are altered in patients with early-stage PDAC. Specifically, we observed a reduction in the level of symmetric dimethyl arginine (SDMA) in plasma sEV proteins derived from patients with early- and late-stage PDAC. Importantly, immunoprecipitation followed by proteomics analysis identified a number of arginine-methylated proteins exclusively present in plasma sEVs derived from patients with early-stage PDAC. These results indicate that arginine methylation patterns in plasma sEVs are potential indicators of PDAC, a new concept meriting further investigation. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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12 pages, 1350 KiB  
Article
Biomarker Analysis from a Phase I/Ib Study of Regorafenib and Nivolumab in Mismatch Repair-Proficient Advanced Refractory Colorectal Cancer
by Dae Won Kim, Young-Chul Kim, Bence P. Kovari, Maria Martinez, Ruoyu Miao, James Yu, Rutika Mehta, Jonathan Strosberg, Iman Imanirad and Richard D. Kim
Cancers 2024, 16(3), 556; https://doi.org/10.3390/cancers16030556 - 28 Jan 2024
Cited by 2 | Viewed by 2266
Abstract
Previously, we reported the modest but durable anticancer activity of regorafenib/nivolumab in mismatch repair-proficient (pMMR) refractory colorectal cancer in our I/Ib study. Our finding suggests the necessity of biomarkers for better selection of patients. Baseline clinical and pathological characteristics, blood and tumor samples [...] Read more.
Previously, we reported the modest but durable anticancer activity of regorafenib/nivolumab in mismatch repair-proficient (pMMR) refractory colorectal cancer in our I/Ib study. Our finding suggests the necessity of biomarkers for better selection of patients. Baseline clinical and pathological characteristics, blood and tumor samples from the patients in the trial were collected and evaluated to discover potential biomarkers. The obtained samples were assessed for immunohistochemistry, ELISA and RNA sequencing. Their correlations with clinical outcome were analyzed. A high albumin level was significantly associated with improved progression-free survival (PFS), overall survival (OS) and disease control. Non-liver metastatic disease showed prolonged PFS and OS. Low regulatory T-cell (Treg) infiltration correlated with prolonged PFS. Low MIP-1β was associated with durable response and improved OS significantly. Upregulation of 23 genes, including CAPN9, NAPSA and ROS1, was observed in the durable disease control group, and upregulation of 10 genes, including MRPS18A, MAIP1 and CMTR2, was associated with a statistically significant improvement of PFS. This study suggests that pretreatment albumin, MIP-1β, non-liver metastatic disease and Treg infiltration may be potential predictive biomarkers of regorafenib/nivolumab in pMMR colorectal cancer. Further studies are needed to confirm these findings. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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21 pages, 1577 KiB  
Article
A Novel Gene List Identifies Tumors with a Stromal-Mesenchymal Phenotype and Worse Prognosis in Gastric Cancer
by Secil Demirkol Canli, Meral Uner, Baris Kucukkaraduman, Diren Arda Karaoglu, Aynur Isik, Nesrin Turhan, Aytekin Akyol, Ismail Gomceli and Ali Osmay Gure
Cancers 2023, 15(11), 3035; https://doi.org/10.3390/cancers15113035 - 2 Jun 2023
Cited by 2 | Viewed by 2413
Abstract
Background: Molecular biomarkers that predict disease progression can help identify tumor subtypes and shape treatment plans. In this study, we aimed to identify robust biomarkers of prognosis in gastric cancer based on transcriptomic data obtained from primary gastric tumors. Methods: Microarray, RNA sequencing, [...] Read more.
Background: Molecular biomarkers that predict disease progression can help identify tumor subtypes and shape treatment plans. In this study, we aimed to identify robust biomarkers of prognosis in gastric cancer based on transcriptomic data obtained from primary gastric tumors. Methods: Microarray, RNA sequencing, and single-cell RNA sequencing-based gene expression data from gastric tumors were obtained from public databases. Freshly frozen gastric tumors (n = 42) and matched FFPE (formalin-fixed, paraffin-embedded) (n = 40) tissues from a Turkish gastric cancer cohort were used for quantitative real-time PCR and immunohistochemistry-based assessments of gene expression, respectively. Results: A novel list of 20 prognostic genes was identified and used for the classification of gastric tumors into two major tumor subgroups with differential stromal gene expression (“Stromal-UP” (SU) and “Stromal-DOWN” (SD)). The SU group had a more mesenchymal profile with an enrichment of extracellular matrix-related gene sets and a poor prognosis compared to the SD group. Expression of the genes within the signature correlated with the expression of mesenchymal markers ex vivo. A higher stromal content in FFPE tissues was associated with shorter overall survival. Conclusions: A stroma-rich, mesenchymal subgroup among gastric tumors identifies an unfavorable clinical outcome in all cohorts tested. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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12 pages, 824 KiB  
Article
Selected Serum Biomarkers (Leptin, Chromogranin A, CA19-9, CEA) in Patients with Pancreatic Neuroendocrine Neoplasm and Associations with Metabolic Syndrome
by Violetta Rosiek, Agnes Bocian-Jastrzębska and Beata Kos-Kudła
Cancers 2023, 15(8), 2348; https://doi.org/10.3390/cancers15082348 - 18 Apr 2023
Cited by 3 | Viewed by 2136
Abstract
Metabolic abnormalities are well-known risk factors for many cancers, even though no clearly established link with pancreatic neuroendocrine neoplasms (PanNENs) has yet been investigated. This research aimed to assess the serum levels of leptin, chromogranin A (CgA), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic [...] Read more.
Metabolic abnormalities are well-known risk factors for many cancers, even though no clearly established link with pancreatic neuroendocrine neoplasms (PanNENs) has yet been investigated. This research aimed to assess the serum levels of leptin, chromogranin A (CgA), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) in patients with PanNENs and to search for associations between PanNENs, these selected serum biomarkers, and metabolic abnormalities in the form of metabolic syndrome (MS). Second, we aimed to investigate whether MS increases the risk of PanNENs. The serum concentrations of biomarkers, metabolic parameters (glucose, cholesterol, triglycerides), and anthropometric measurements (weight, height, BMI) were assessed in 106 patients with PanNENs and 40 healthy volunteers. Patients with PanNENs showed higher serum concentrations of CA19-9, CEA, and CgA in comparison to controls (p < 0.001, p = 0.042, and p = 0.025, respectively). Statistically significant differences in CEA levels were found in PanNENs patients with MS (p = 0.043). PanNENs patients with a BMI ≥ 25 kg/m2 and who were female exhibited significantly higher leptin levels (p < 0.001 and p = 0.013, respectively). Additionally, this study reflects the importance of determining markers. Future research should focus on understanding the impact of metabolic disturbances on PanNENs and accounting for the relationship between PanNENs and MS, such as other malignancies. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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18 pages, 1530 KiB  
Article
Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy—A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study
by Nikolaos Spathas, Anna C. Goussia, Georgia-Angeliki Koliou, Helen Gogas, Flora Zagouri, Anna Batistatou, Antonia V. Charchanti, Alexandra Papoudou-Bai, Mattheos Bobos, Sofia Chrisafi, Kyriakos Chatzopoulos, Ioannis Kostopoulos, Triantafyllia Koletsa, Petroula Arapantoni, Dimitrios Pectasides, Eleni Galani, Angelos Koutras, George Zarkavelis, Emmanouil Saloustros, Dimitrios Bafaloukos, Charisios Karanikiotis, Iliada Bompolaki, Gerasimos Aravantinos, Amanda Psyrri, Evangelia Razis, Anna Koumarianou, Eleni Res, Helena Linardou and George Fountzilasadd Show full author list remove Hide full author list
Cancers 2022, 14(22), 5635; https://doi.org/10.3390/cancers14225635 - 16 Nov 2022
Cited by 5 | Viewed by 2231
Abstract
Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and [...] Read more.
Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients’ tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm2 (DFS: HR = 0.58, p = 0.011 and HR = 0.65, p = 0.034 and OS: HR = 0.63, p = 0.043 and HR = 0.58, p = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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Review

Jump to: Research

17 pages, 1266 KiB  
Review
The Antithetic Roles of IQGAP2 and IQGAP3 in Cancers
by Fei Song, Qingqing Dai, Marc-Oliver Grimm and Daniel Steinbach
Cancers 2023, 15(4), 1115; https://doi.org/10.3390/cancers15041115 - 9 Feb 2023
Cited by 14 | Viewed by 3250
Abstract
The scaffold protein family of IQ motif-containing GTPase-activating proteins (IQGAP1, 2, and 3) share a high degree of homology and comprise six functional domains. IQGAPs bind and regulate the cytoskeleton, interact with MAP kinases and calmodulin, and have GTPase-related activity, as well as [...] Read more.
The scaffold protein family of IQ motif-containing GTPase-activating proteins (IQGAP1, 2, and 3) share a high degree of homology and comprise six functional domains. IQGAPs bind and regulate the cytoskeleton, interact with MAP kinases and calmodulin, and have GTPase-related activity, as well as a RasGAP domain. Thus, IQGAPs regulate multiple cellular processes and pathways, affecting cell division, growth, cell–cell interactions, migration, and invasion. In the past decade, significant evidence on the function of IQGAPs in signal transduction during carcinogenesis has emerged. Compared with IQGAP1, IQGAP2 and IQGAP3 were less analyzed. In this review, we summarize the different signaling pathways affected by IQGAP2 and IQGAP3, and the antithetic roles of IQGAP2 and IQGAP3 in different types of cancer. IQGAP2 expression is reduced and plays a tumor suppressor role in most solid cancer types, while IQGAP3 is overexpressed and acts as an oncogene. In lymphoma, for example, IQGAPs have partially opposite functions. There is considerable evidence that IQGAPs regulate a multitude of pathways to modulate cancer processes and chemoresistance, but some questions, such as how they trigger this signaling, through which domains, and why they play opposite roles on the same pathways, are still unanswered. Full article
(This article belongs to the Special Issue New Biomarkers in Cancers 2nd Edition)
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