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Development of Biomarker-Driven Targeted Therapies in Cancers

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (10 February 2023) | Viewed by 5361

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Special Issue Editor

Dr. Anne Mary Noonan

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Guest Editor

Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA
Interests: gastrointestinal cancers; drug development; hepatocellular carcinoma; pancreatic adenocarcinoma; biomarkers

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit articles to our Special Edition entitled “Biomarker-Driven Targeted Therapies in Cancers”. Significant progress has been made in recent decades for certain cancer types where specific molecular alterations drive cancer progression. The development of imatinib targeting BCR-ABL, c-KIT, and PDGFRA revolutionized the treatment of chronic myeloid leukemia and GIST and paved the way for modern targeted therapies. As a result of biomarker-driven targeted therapies, the prognosis of malignancies such as HER-2 positive breast cancers and BRAF-mutated melanoma has improved greatly. However, elucidating signaling networks for many other malignancies has been more challenging, with constellations of signaling pathways often being involved, making the development of targeted therapies more difficult for certain tumors. Thus, a multi-pronged targeted approach may be needed with exploration of targets beyond those found by next-generation sequencing.

This Special Issue aims to describe current research surrounding the development of the next generation of biomarker-driven targeted therapies for cancer.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

New strategies to target known driver biomarkers
New drugs for new targets in cancer
Novel targets
Circulating tumor DNA as a target
Assessing response to targeted therapies
Challenges in dosing targeted therapies

We look forward to receiving your contributions.

Dr. Anne Mary Noonan
Guest Editor

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 short 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. Pharmaceutics is an international peer-reviewed open access monthly 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

Novel molecular profiling
Drug design
Microenvironment
Antibody–drug conjugates
In vitro study
In vivo study
Genetic mutations
Predictive markers

Published Papers (3 papers)

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Research

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15 pages, 1049 KiB

Open AccessArticle

Therapeutic Performance Evaluation of ²¹³Bi-Labelled Aminopeptidase N (APN/CD13)-Affine NGR-Motif ([²¹³Bi]Bi-DOTAGA-cKNGRE) in Experimental Tumour Model: A Treasured Tailor for Oncology

by Zita Képes, Viktória Arató, Judit P. Szabó, Barbara Gyuricza, Dániel Szücs, István Hajdu, Anikó Fekete, Frank Bruchertseifer, Dezső Szikra and György Trencsényi

Pharmaceutics 2023, 15(2), 491; https://doi.org/10.3390/pharmaceutics15020491 - 1 Feb 2023

Cited by 1 | Viewed by 1428

Abstract

Since NGR-tripeptides (asparagine-glycine-arginine) selectively target neoangiogenesis-associated Aminopeptidase N (APN/CD13) on cancer cells, we aimed to evaluate the in vivo tumour targeting capability of radiolabelled, NGR-containing, ANP/CD13-selective [²¹³Bi]Bi-DOTAGA-cKNGRE in CD13pos. HT1080 fibrosarcoma-bearing severe combined immunodeficient CB17 mice. 10 ± 1 days after cancer cell inoculation, positron emission tomography (PET) was performed applying [⁶⁸Ga]Ga-DOTAGA-cKNGRE for tumour verification. On the 7th, 8th, 10th and 12th days the treated group of tumourous mice were intraperitoneally administered with 4.68 ± 0.10 MBq [²¹³Bi]Bi-DOTAGA-cKNGRE, while the untreated tumour-bearing animals received 150 μL saline solution. In addition to body weight (BW) and tumour volume measurements, ex vivo biodistribution studies were conducted 30 and 90 min postinjection (pi.). The following quantitative standardised uptake values (SUV) confirmed the detectability of the HT1080 tumours: SUV_mean and SUV_max: 0.37 ± 0.09 and 0.86 ± 0.14, respectively. Although no significant difference (p ≤ 0.05) was encountered between the BW of the treated and untreated mice, their tumour volumes measured on the 9th, 10th and 12th days differed significantly (p ≤ 0.01). Relatively higher [²¹³Bi]Bi-DOTAGA-cKNGRE accumulation of the HT1080 neoplasms (%ID/g: 0.80 ± 0.16) compared with the other organs at 90 min time point yields better tumour-to-background ratios. Therefore, the therapeutic application of APN/CD13-affine [²¹³Bi]Bi-DOTAGA- cKNGRE seems to be promising in receptor-positive fibrosarcoma treatment. Full article

(This article belongs to the Special Issue Development of Biomarker-Driven Targeted Therapies in Cancers)

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13 pages, 2954 KiB

Open AccessArticle

Identification of Prognostic and Predictive Biomarkers and Druggable Targets among 205 Antioxidant Genes in 21 Different Tumor Types via Data-Mining

by Nadire Özenver and Thomas Efferth

Pharmaceutics 2023, 15(2), 427; https://doi.org/10.3390/pharmaceutics15020427 - 28 Jan 2023

Cited by 2 | Viewed by 1585

Abstract

(1) Background: Oxidative stress is crucial in carcinogenesis and the response of tumors to treatment. Antioxidant genes are important determinants of resistance to chemotherapy and radiotherapy. We hypothesized that genes involved in the oxidative stress response may be valuable as prognostic biomarkers for the survival of cancer patients and as druggable targets. (2) Methods: We mined the KM Plotter and TCGA Timer2.0 Cistrome databases and investigated 205 antioxidant genes in 21 different tumor types within the context of this investigation. (3) Results: Of 4347 calculations with Kaplan–Meier statistics, 84 revealed statistically significant correlations between high gene expression and worse overall survival (p < 0.05; false discovery rate ≤ 5%). The tumor types for which antioxidant gene expression was most frequently correlated with worse overall survival were renal clear cell carcinoma, renal papillary cell carcinoma, and hepatocellular carcinoma. Seventeen genes were clearly overexpressed in tumors compared to their corresponding normal tissues (p < 0.001), possibly qualifying them as druggable targets (i.e., ALOX5, ALOX5AP, EPHX4, G6PD, GLRX3, GSS, PDIA4, PDIA6, PRDX1, SELENOH, SELENON, STIP1, TXNDC9, TXNDC12, TXNL1, TXNL4A, and TXNRD1). (4) Conclusions: We concluded that a sub-set of antioxidant genes might serve as prognostic biomarkers for overall survival and as druggable targets. Renal and liver tumors may be the most suitable entities for this approach. Full article

(This article belongs to the Special Issue Development of Biomarker-Driven Targeted Therapies in Cancers)

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Review

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19 pages, 617 KiB

Open AccessReview

Cancer-Associated Membrane Protein as Targeted Therapy for Bladder Cancer

by Adlina Roslan, Nurshahira Sulaiman, Khairul Asri Mohd Ghani and Armania Nurdin

Pharmaceutics 2022, 14(10), 2218; https://doi.org/10.3390/pharmaceutics14102218 - 18 Oct 2022

Cited by 1 | Viewed by 1858

Abstract

Bladder cancer (BC) recurrence is one of the primary clinical problems encountered by patients following chemotherapy. However, the mechanisms underlying their resistance to chemotherapy remain unclear. Alteration in the pattern of membrane proteins (MPs) is thought to be associated with this recurrence outcome, often leading to cell dysfunction. Since MPs are found throughout the cell membrane, they have become the focus of attention for cancer diagnosis and treatment. Identifying specific and sensitive biomarkers for BC, therefore, requires a major collaborative effort. This review describes studies on membrane proteins as potential biomarkers to facilitate personalised medicine. It aims to introduce and discuss the types and significant functions of membrane proteins as potential biomarkers for future medicine. Other types of biomarkers such as DNA-, RNA- or metabolite-based biomarkers are not included in this review, but the focus is mainly on cell membrane surface protein-based biomarkers. Full article

(This article belongs to the Special Issue Development of Biomarker-Driven Targeted Therapies in Cancers)

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