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Cancers
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Cancer Biomarkers—Detection and Evaluation of Response to Therapy
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Cancer Biomarkers—Detection and Evaluation of Response to Therapy

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

Deadline for manuscript submissions: 30 June 2025 | Viewed by 5281

Special Issue Editors

Dr. Giulio Francia

E-Mail Website
Guest Editor
Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX, USA
Interests: chemotherapy; cancer biology; metronomic chemotherapy; metastasis; immunotherapy
Dr. Jianying Zhang

E-Mail Website
Guest Editor
Border Biomedical Research Center, University of Texas at El Paso, El Paso, TX, USA
Interests: cancer biomarkers; cancer autoimmunity (auto-antibodies)

Special Issue Information

Dear Colleagues,

Cancer biomarkers are increasingly important in the detection of earlier stages of disease; they are essential, and still in need of discovery, in the optimal dosing of anti-cancer drugs, predicting treatment-related toxicity, and selecting therapies that can most benefit either individual patients or subgroups with a particular cancer.

This Special issue will explore past and present biomarkers, novel biomarkers, and the use of biomarkers with different diagnostic and treatment options to improve the detection and management of cancer.

Dr. Giulio Francia
Dr. Jianying Zhang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • biomarkers
  • cancer detection
  • biomarkers of response to antineoplastic drugs
  • biomarkers of resistance to chemotherapy
  • biomarkers for targeted therapies

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Published Papers (5 papers)

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Research

18 pages, 3449 KiB  
Article
Impact of Neoadjuvant Treatment on Target Expression in Rectal Cancer for Near-Infrared Tumor Imaging
by Elham Zonoobi, Lisanne K. A. Neijenhuis, Annelieke A. Lemij, Daan G. J. Linders, Ehsan Nazemalhosseini-Mojarad, Shadhvi S. Bhairosingh, N. Geeske Dekker-Ensink, Ronald L. P. van Vlierberghe, Koen C. M. J. Peeters, Fabian A. Holman, Rob A. E. M. Tollenaar, Denise E. Hilling, A. Stijn L. P. Crobach, Alexander L. Vahrmeijer and Peter J. K. Kuppen
Cancers 2025, 17(12), 1958; https://doi.org/10.3390/cancers17121958 - 12 Jun 2025
Viewed by 229
Abstract
Background: Rectal cancer (RC) patients with a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) may qualify for a watch-and-wait (W&W) approach. However, a 20–30% local tumor regrowth rate highlights challenges in identifying true responders. This study explores markers for future near-infrared fluorescence [...] Read more.
Background: Rectal cancer (RC) patients with a clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) may qualify for a watch-and-wait (W&W) approach. However, a 20–30% local tumor regrowth rate highlights challenges in identifying true responders. This study explores markers for future near-infrared fluorescence tumor imaging by endoscopy to differentiate responders and the effect of nCRT on their expression. Methods: RC samples (n = 51) were collected from both pre-treatment biopsies and corresponding post-treatment surgical specimens. Samples were categorized by treatment response and determined using tumor regression grade (TRG) scoring. Immunohistochemistry assessed the expression of CEA, EpCAM, EGFR, and c-MET in tumors and adjacent normal tissues. Expression levels were quantified using H-scores (0–3), combining the percentage and intensity of stained cells. Pre- and post-treatment H-scores were compared to evaluate the impact of nCRT. Results: CEA, EpCAM, and c-MET were overexpressed in tumor tissue as compared to adjacent healthy mucosa in 100% (51/51), 98.4% (50/51), and 92% (47/51) of tumor biopsies, respectively, while EGFR showed no overexpression. A tumor-to-normal (T/N) ratio ≥ 2 was considered sufficient for differentiation in molecular fluorescence imaging. In pre-treatment biopsy samples, c-MET showed the highest T/N expression ratio (53% of the samples ≥ 2), followed by CEA (26.3%) and EpCAM (16%). Following nCRT treatment, CEA and c-MET maintained a ≥ 2 differential expression in 45% of all samples, whereas EpCAM exhibited this difference in only 9.2% of cases. Neoadjuvant therapy even significantly improved the T/N expression ratio for CEA and c-MET (p < 0.01) and EpCAM (p < 0.05), while EGFR expression remained lower than adjacent normal tissue. Significant increases in all marker expressions were observed in minimal responders (TRG4/5, p < 0.01–0.001), while near-complete responders (TRG2) exhibited non-significant changes in CEA, c-MET, and EGFR expression. Conclusions: c-MET and CEA emerged as optimal tumor imaging targets, showing sustained differential expression after nCRT. In vivo fluorescence-guided endoscopy using probes against these markers could play a role in future clinical decision-making. Full article
(This article belongs to the Special Issue Cancer Biomarkers—Detection and Evaluation of Response to Therapy)
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29 pages, 4316 KiB  
Article
Development of a Novel Biomarker Platform for Profiling Key Protein–Protein Interactions to Predict the Efficacy of BH3-Mimetic Drugs
by Andrew J. Kinloch, Faiyaz Rahman, Bahriye Karakas, Muhammad Shahid, Bora Lim, Stephanie J. Bouley, James A. Walker, Erinna F. Lee, Walter D. Fairlie, Kevin R. Kelly and Michael H. Cardone
Cancers 2025, 17(11), 1852; https://doi.org/10.3390/cancers17111852 - 31 May 2025
Viewed by 655
Abstract
One of the hallmarks of cancer cells is their failure to respond to the cellular mechanism of apoptosis. The B-cell lymphoma 2 (BCL-2) family of proteins regulate apoptosis. Their ability to do so can be measured using several methods that in turn anticipate [...] Read more.
One of the hallmarks of cancer cells is their failure to respond to the cellular mechanism of apoptosis. The B-cell lymphoma 2 (BCL-2) family of proteins regulate apoptosis. Their ability to do so can be measured using several methods that in turn anticipate the fate of the cancer cell in response to apoptosis-inducing treatment. These assays ultimately identify the readiness of the cancer cell to undergo apoptosis, which is referred to as the mitochondrial priming state. These metrics, however, have been challenging to implement in the clinic. Methods: Here, we describe a unique method that relies on a panel of novel conformation-specific antibodies (termed PRIMAB) that can directly measure the mitochondrial priming state. These reagents are highly specific for complexes of their corresponding pro-survival protein interactions with the pro-apoptotic protein BIM. These BIM-containing heterodimeric complexes have long been established as hallmarks of primed cancer cells. Results: Using clinically amenable assay formats, PRIMABs were shown to detect the presence of these anti-apoptotic–pro-apoptotic complexes and their disruption by BH3-mimetic drugs. Moreover, PRIMABs were able to detect a shift in priming status following BH3-mimetic treatment, a factor associated with resistance to these drugs. In a panel of AML patient samples, we report a wide range of priming levels for each PRIMAB complex, demonstrating the potential for heterogeneity in responses. We also show that PRIMABs could be predictive of outcomes for AML patients following cytarabine-based treatment. Conclusions: PRIMABs provide novel and useful tools for cancer research and for clinical implementation as reagents providing predictive tests for treatment response. Full article
(This article belongs to the Special Issue Cancer Biomarkers—Detection and Evaluation of Response to Therapy)
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14 pages, 1370 KiB  
Article
Circulating microRNAs as a Prognostic Tool to Determine Treatment Efficacy in Lung Cancer Patients Undergoing Pembrolizumab PD-1 Blockade Immunotherapy
by Mishfak A. Mohamed Mansoor, Xiang Zhu, Sarah Aslam Ashiqueali, Md Tanjim Alam, Hanna Winiarska, Pawel Pazdrowski, Filip Kaminski, Alicja Copik, Michal M. Masternak and Barbara Kuznar-Kaminska
Cancers 2024, 16(24), 4202; https://doi.org/10.3390/cancers16244202 - 17 Dec 2024
Viewed by 1345
Abstract
Background: Pembrolizumab has recently emerged as a PD-1 blockade immunotherapy treatment for lung cancer. It is critical that such treatment strategies for lung cancer should be chosen not only on the basis of histopathological features and the expression of targetable cell surface proteins [...] Read more.
Background: Pembrolizumab has recently emerged as a PD-1 blockade immunotherapy treatment for lung cancer. It is critical that such treatment strategies for lung cancer should be chosen not only on the basis of histopathological features and the expression of targetable cell surface proteins (such as PD-1), but should rather be selected based on other determinants of treatment success or risk factors for poor prognosis. One method to forecast cancer trajectory is the identification of biomolecular signatures such as microRNAs (miRNAs), non-protein-coding RNA molecules that play a regulatory role in gene expression by modulating the translation or stability of messenger RNA. Methods: To find out which miRNAs have an important influence on anti-PD-1 treatment outcomes, we evaluated miRNA levels in sera from 38 lung cancer patients undergoing 3 months of pembrolizumab treatment. We selected a panel of miRNAs previously shown to be involved in lung cancer or PD-1 signaling and performed qPCR analysis. Results: Overall, we observed a significant decrease in the levels of miR126-5p (4-fold), let-7a (5-fold), miR133a-3p (4-fold), miR3615 (2-fold), miR4516 (3-fold), miR16 (3-fold), miR34c-5p (2-fold), miR20b-5p (5-fold), miR106b-5p (5-fold), miR146a-5p (3-fold) and miR181b-5p (3-fold) in response to treatment indicating effectiveness of immunotherapy. Within our selected panel of miRNAs, we identified two markers relevant to cancer prognosis: miR-217, which is negatively associated with patient survival, and let-7a, which is positively associated with patient survival. Conclusions: Our findings suggest that circulating miRNAs can be used for future treatment evaluation and lung cancer prognosis, with potential as therapeutic targets. Full article
(This article belongs to the Special Issue Cancer Biomarkers—Detection and Evaluation of Response to Therapy)
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11 pages, 1876 KiB  
Article
Reduction of Blood Oxidative Stress Following Colorectal Cancer Resection
by Katsuji Sawai, Takanori Goi, Youhei Kimura and Kenji Koneri
Cancers 2024, 16(20), 3550; https://doi.org/10.3390/cancers16203550 - 21 Oct 2024
Cited by 1 | Viewed by 1005
Abstract
Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a [...] Read more.
Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a primary source of oxidative stress, would reduce blood levels of reactive oxygen metabolite derivatives (d-ROMs), a marker of oxidative stress, and biologic antioxidant potential (BAP) levels, a marker of antioxidant potential. Methods: This study included 123 patients who underwent radical resection for colorectal cancer. d-ROM and BAP levels were measured before and one month after surgery. Results: The clinicopathological analysis showed a correlation between preoperative d-ROM levels and tumor size (p < 0.001). This study confirmed a significant reduction in d-ROM levels following tumor resection, indicating reduced systemic oxidative stress. The reduction was significant in stages II and III, but not in stage I. The d-ROM ratio before and after tumor resection was significantly higher in cases with positive lymph node metastasis and larger tumor size. BAP levels showed no significant changes post-surgery. Conclusions: These results suggest that d-ROMs could serve as a valuable biomarker for monitoring tumor burden and surgical efficacy in patients with colorectal cancer. Full article
(This article belongs to the Special Issue Cancer Biomarkers—Detection and Evaluation of Response to Therapy)
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12 pages, 1529 KiB  
Article
Can Delta Radiomics Improve the Prediction of Best Overall Response, Progression-Free Survival, and Overall Survival of Melanoma Patients Treated with Immune Checkpoint Inhibitors?
by Felix Peisen, Annika Gerken, Alessa Hering, Isabel Dahm, Konstantin Nikolaou, Sergios Gatidis, Thomas K. Eigentler, Teresa Amaral, Jan H. Moltz and Ahmed E. Othman
Cancers 2024, 16(15), 2669; https://doi.org/10.3390/cancers16152669 - 26 Jul 2024
Cited by 2 | Viewed by 1379 | Correction
Abstract
Background: The prevalence of metastatic melanoma is increasing, necessitating the identification of patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker based on the segmentation of all metastases at baseline and the first follow-up CT for the [...] Read more.
Background: The prevalence of metastatic melanoma is increasing, necessitating the identification of patients who do not benefit from immunotherapy. This study aimed to develop a radiomic biomarker based on the segmentation of all metastases at baseline and the first follow-up CT for the endpoints best overall response (BOR), progression-free survival (PFS), and overall survival (OS), encompassing various immunotherapies. Additionally, this study investigated whether reducing the number of segmented metastases per patient affects predictive capacity. Methods: The total tumour load, excluding cerebral metastases, from 146 baseline and 146 first follow-up CTs of melanoma patients treated with first-line immunotherapy was volumetrically segmented. Twenty-one random forest models were trained and compared for the endpoints BOR; PFS at 6, 9, and 12 months; and OS at 6, 9, and 12 months, using as input either only clinical parameters, whole-tumour-load delta radiomics plus clinical parameters, or delta radiomics from the largest ten metastases plus clinical parameters. Results: The whole-tumour-load delta radiomics model performed best for BOR (AUC 0.81); PFS at 6, 9, and 12 months (AUC 0.82, 0.80, and 0.77); and OS at 6 months (AUC 0.74). The model using delta radiomics from the largest ten metastases performed best for OS at 9 and 12 months (AUC 0.71 and 0.75). Although the radiomic models were numerically superior to the clinical model, statistical significance was not reached. Conclusions: The findings indicate that delta radiomics may offer additional value for predicting BOR, PFS, and OS in metastatic melanoma patients undergoing first-line immunotherapy. Despite its complexity, volumetric whole-tumour-load segmentation could be advantageous. Full article
(This article belongs to the Special Issue Cancer Biomarkers—Detection and Evaluation of Response to Therapy)
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