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Cancers
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Pre-Clinical Studies of Personalized Medicine for Cancer Research
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Pre-Clinical Studies of Personalized Medicine for Cancer Research

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 37731

Special Issue Editor

Dr. Nuno Vale

E-Mail Website
Guest Editor
Department of Community Medicine, Health Information and Decision, Faculty of Medicine, University of Porto, Rua Dr. Plácido da Costa, 4200-450 Porto, Portugal
Interests: in silico pharmacology; PBPK; drug metabolism; drug combination; drug delivery; peptides; ADME; DMPK; pharmacokinetic
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pre-clinical studies of personalized medicine for cancer involve the exploration and development of targeted therapies and treatment strategies that are tailored to the unique genetic and molecular characteristics of an individual's cancer. These studies play a crucial role in advancing the field of oncology by providing valuable insights into the efficacy, safety, and potential side effects of personalized treatments before they are tested in human clinical trials.

This Special Issue is dedicated to key aspects of pre-clinical studies for personalized medicine in cancer research, for patent-derived models (which can include cell lines, xenografts (tumors grown in mice using patient-derived cells), or organoids (3D cultures of cancer cells that mimic the original tumor)), genomic profiling (specific mutations, alterations, and biomarkers that may be targeted by personalized therapies), drug screening (targeted therapies, immunotherapies, and conventional chemotherapeutics, or drug repurposing), biomarker validation (identified through genomic profiling), combination therapies (synergies between different drugs or treatment modalities), toxicity and safety assessment (understanding the therapeutic window and ensuring that the treatment is safe for patients), mechanistic studies (how specific drugs interact with molecular targets and pathways within cancer cells), tumor heterogeneity (pre-clinical studies taking into account the heterogeneity of tumors, recognizing that different regions of a tumor may have distinct genetic profiles), animal studies (understanding how treatments perform in a whole organism and providing insights into potential systemic effects), and data analysis interpretation (statistical methods and bioinformatics play a crucial role in the effectiveness and safety of personalized treatments).

In this Special Issue, original articles and reviews would be highly appreciated.

I look forward to receiving your contributions.

Dr. Nuno Vale
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 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

  • patient-derived models
  • genomic profiling
  • drug screening
  • biomarker validation
  • combination therapies
  • mechanistic studies
  • tumor heterogeneity
  • data analysis and interpretation

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Published Papers (8 papers)

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Research

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11 pages, 1109 KiB  
Article
The Safety and Suitability of DNA Sequencing of Tissue Biopsies Performed on Patients Referred to a Phase I Unit
by Angela Esposito, Edoardo Crimini, Carmen Criscitiello, Carmen Belli, Roberta Scafetta, Raimondo Scalia, Grazia Castellano, Elisa Giordano, Jalissa Katrini, Liliana Ascione, Luca Boscolo Bielo, Matteo Repetto, Antonio Marra, Dario Trapani, Gianluca Maria Varano, Daniele Maiettini, Paolo Della Vigna, Franco Orsi, Elena Guerini Rocco, Nicola Fusco and Giuseppe Curiglianoadd Show full author list remove Hide full author list
Cancers 2024, 16(24), 4252; https://doi.org/10.3390/cancers16244252 - 20 Dec 2024
Viewed by 560
Abstract
Background: Early-phase clinical trials offer a unique opportunity for patients with cancer. These trials often mandate biopsies to collect tumor tissue for research purposes, requiring patients to undergo invasive procedures. Some trials mandate molecular prescreening, but the success of these analyses relies on [...] Read more.
Background: Early-phase clinical trials offer a unique opportunity for patients with cancer. These trials often mandate biopsies to collect tumor tissue for research purposes, requiring patients to undergo invasive procedures. Some trials mandate molecular prescreening, but the success of these analyses relies on the quality and quantity of the tested materials. Additionally, bioptic procedures may result in complications. Methods: We retrospectively examined the records of patients referred to the Early Drug Development (EDD) Unit of the European Institute of Oncology who underwent biopsies for research purposes between January 2014 and December 2022. Our objective was to assess the safety of biopsy procedures and adequacy of the samples for NGS testing. Results: In total, 355 out of 731 patients (48.6%) underwent protocol-mandated biopsies. The most frequent sites of biopsy were the liver, lymph nodes, skin, and breast. Histological diagnosis was achieved in 349 (98%) patients, and NGS testing was successfully conducted in 111/127 (88.4%) cases. Of the 16 unsuccessful NGS attempts, 9 were performed on liver tissue. Unsuccessful NGS testing was attributed to poor sample quality and/or quantity, and the success rate varied significantly based on the specific tests attempted. Complications occurred in a small proportion of patients (4.8%), and none were serious. Conclusions: The non-negligible failure rate of NGS testing highlights the crucial need for implementing specific guidelines and Standard Operating Procedures for samples intended for NGS. With the use of a risk-based biopsy framework to guide clinical decisions, procedure-related complications may be minimized. Full article
(This article belongs to the Special Issue Pre-Clinical Studies of Personalized Medicine for Cancer Research)
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19 pages, 6601 KiB  
Article
CD103+ cDC1 Dendritic Cell Vaccine Therapy for Osteosarcoma Lung Metastases
by Yuanzheng Yang, Yifan Zhou, Jian Wang, You Zhou, Stephanie S. Watowich and Eugenie S. Kleinerman
Cancers 2024, 16(19), 3251; https://doi.org/10.3390/cancers16193251 - 24 Sep 2024
Viewed by 4020
Abstract
Background: We generated a CD103+DC vaccine using K7M3 OS cell lysates (cDCV) and investigated its ability to induce regression of primary tumors, established lung metastases, and a systemic immune response. Methods: A bilateral tumor model was used to assess cDCV therapy [...] Read more.
Background: We generated a CD103+DC vaccine using K7M3 OS cell lysates (cDCV) and investigated its ability to induce regression of primary tumors, established lung metastases, and a systemic immune response. Methods: A bilateral tumor model was used to assess cDCV therapy efficacy and systemic immunity induction. K7M3 cells were injected into mice bilaterally. Right-sided tumors received PBS (control) or cDCV. Left-sided tumors were untreated. Tumor growth was compared between the vaccine-treated and untreated tumor on the contralateral side and compared to the control group. The immune cell profiles of the tumors, and tumor-draining lymph nodes (TdLNs) and spleen were evaluated. To determine the efficacy of systemic cDCV therapy against established lung metastases, K7M3 cells were injected intratibially. Leg amputation was performed 5 weeks later. Mice were treated intravenously with PBS or cDCV and euthanized 6 weeks later. Lungs, TdLNs and spleen were collected. The number and size of the lung nodules were quantified. The immune cell profile of tumor, and lymph nodes and spleen were also evaluated. Using this same model, we evaluated the effect of cDCV + anti-CTLA-4. Results: cDCV therapy inhibited the treated and untreated tumors and increased the number of T-cells in these tumors and the lymph nodes compared to control-treated mice. Systemic cDCV therapy administered following amputation decreased the size and number of lung metastases, and increased T-cell numbers in the tumor and lymph nodes. Combining anti-CTLA-4 with cDCV therapy increased cDCV efficacy against lung metastases. Conclusions: Intratumor cDCV generated a systemic immune response inhibiting the growth of both the treated and untreated tumors, with increased T-cells in the tumor and lymph nodes. Systemic cDCV was effective against established lung metastases. Efficacy was increased by anti-CTLA4. cDCVs may provide a novel therapeutic approach for relapsed/metastatic OS patients. Full article
(This article belongs to the Special Issue Pre-Clinical Studies of Personalized Medicine for Cancer Research)
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Review

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30 pages, 1495 KiB  
Review
Advances in Personalized Oncology
by Hiba Mechahougui, James Gutmans, Gina Colarusso, Roumaïssa Gouasmi and Alex Friedlaender
Cancers 2024, 16(16), 2862; https://doi.org/10.3390/cancers16162862 - 16 Aug 2024
Cited by 3 | Viewed by 2368
Abstract
Advances in next-generation sequencing (NGS) have catalyzed a paradigm shift in cancer treatment, steering the focus from conventional, organ-specific protocols to precision medicine. Emerging targeted therapies offer a cutting-edge approach to cancer treatment, while companion diagnostics play an essential role in aligning therapeutic [...] Read more.
Advances in next-generation sequencing (NGS) have catalyzed a paradigm shift in cancer treatment, steering the focus from conventional, organ-specific protocols to precision medicine. Emerging targeted therapies offer a cutting-edge approach to cancer treatment, while companion diagnostics play an essential role in aligning therapeutic choices with specific molecular changes identified through NGS. Despite these advances, interpreting the clinical implications of a rapidly expanding catalog of genetic mutations remains a challenge. The selection of therapies in the presence of multiple mutations requires careful clinical judgment, supported by quality-centric genomic testing that emphasizes actionable mutations. Molecular tumor boards can play an increasing role in assimilating genomic data into clinical trials, thereby refining personalized treatment approaches and improving patient outcomes. Full article
(This article belongs to the Special Issue Pre-Clinical Studies of Personalized Medicine for Cancer Research)
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31 pages, 1646 KiB  
Review
Glioblastoma Standard of Care: Effects on Tumor Evolution and Reverse Translation in Preclinical Models
by Louis T. Rodgers, John L. Villano, Anika M. S. Hartz and Björn Bauer
Cancers 2024, 16(15), 2638; https://doi.org/10.3390/cancers16152638 - 24 Jul 2024
Cited by 1 | Viewed by 2762
Abstract
Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past [...] Read more.
Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment—surgery, radiation, and chemotherapy—on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM. Full article
(This article belongs to the Special Issue Pre-Clinical Studies of Personalized Medicine for Cancer Research)
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19 pages, 1722 KiB  
Review
Glutamine Supplementation as an Anticancer Strategy: A Potential Therapeutic Alternative to the Convention
by Hayato Muranaka, Rasaq Akinsola, Sandrine Billet, Stephen J. Pandol, Andrew E. Hendifar, Neil A. Bhowmick and Jun Gong
Cancers 2024, 16(5), 1057; https://doi.org/10.3390/cancers16051057 - 5 Mar 2024
Cited by 5 | Viewed by 12173
Abstract
Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer [...] Read more.
Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer treatment, emphasizing the critical role of glutamine metabolism in cancer progression and therapy. Glutamine antagonism, aiming to disrupt tumor growth by targeting critical metabolic pathways, is challenged by the adaptive nature of cancer cells and the complex metabolic microenvironment, potentially compromising its therapeutic efficacy. In contrast, glutamine supplementation supports immune function, improves gut integrity, alleviates treatment-related toxicities, and improves patient well-being. Moreover, recent studies highlighted its contributions to epigenetic regulation within cancer cells and its potential to bolster anti-cancer immune functions. However, glutamine implementation necessitates careful consideration of potential interactions with ongoing treatment regimens and the delicate equilibrium between supporting normal cellular function and promoting tumorigenesis. By critically assessing the implications of both glutamine antagonism strategies and glutamine supplementation, this review aims to offer comprehensive insights into potential therapeutic strategies targeting glutamine metabolism for effective cancer management. Full article
(This article belongs to the Special Issue Pre-Clinical Studies of Personalized Medicine for Cancer Research)
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11 pages, 265 KiB  
Review
Supplement Use and Increased Risks of Cancer: Unveiling the Other Side of the Coin
by Parnian Jabbari, Omid Yazdanpanah, David J. Benjamin and Arash Rezazadeh Kalebasty
Cancers 2024, 16(5), 880; https://doi.org/10.3390/cancers16050880 - 22 Feb 2024
Cited by 5 | Viewed by 7699
Abstract
There is a rising trend in the consumption of dietary supplements, especially among adults, with the purpose of improving health. While marketing campaigns tout the potential health benefits of using dietary supplements, it is critical to evaluate the potential harmful effects associated with [...] Read more.
There is a rising trend in the consumption of dietary supplements, especially among adults, with the purpose of improving health. While marketing campaigns tout the potential health benefits of using dietary supplements, it is critical to evaluate the potential harmful effects associated with these supplements as well. The majority of the scarce research on the potential harmful effects of vitamins focuses on the acute or chronic toxicities associated with the use of dietary supplements. Quality research is still required to further investigate the risks of long-term use of dietary supplements, especially the risk of developing cancers. The present review concentrates on studies that have investigated the association between the risk of developing cancers and associated mortality with the risk of dietary supplements. Such an association has been reported for several vitamins, minerals, and other dietary supplements. Even though several of these studies come with their own shortcomings and critics, they must draw attention to further investigate long-term adverse effects of dietary supplements and advise consumers and healthcare providers to ponder the extensive use of dietary supplements. Full article
(This article belongs to the Special Issue Pre-Clinical Studies of Personalized Medicine for Cancer Research)
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Graphical abstract

22 pages, 2532 KiB  
Review
Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy
by Chloe Springer, Danish Humayun and Rachid Skouta
Cancers 2024, 16(3), 647; https://doi.org/10.3390/cancers16030647 - 2 Feb 2024
Cited by 17 | Viewed by 5949
Abstract
Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced cell death, known as cuproptosis, and its potential health and disease implications, including cancer therapy. Copper [...] Read more.
Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced cell death, known as cuproptosis, and its potential health and disease implications, including cancer therapy. Copper ionophores, such as elesclomol and disulfiram, increase intracellular copper levels. This elevation triggers oxidative stress and subsequent cell death, offering potential implications in cancer therapy. Additionally, copper ionophores disrupt mitochondrial respiration and protein lipoylation, further contributing to copper toxicity and cell death. Potential targets and biomarkers are identified, as copper can be targeted to those proteins to trigger cuproptosis. The role of copper in different cancers is discussed to understand targeted cancer therapies using copper nanomaterials, copper ionophores, and copper chelators. Furthermore, the role of copper is explored through diseases such as Wilson and Menkes disease to understand the physiological mechanisms of copper. Exploring cuproptosis presents an opportunity to improve treatments for copper-related disorders and various cancers, with the potential to bring significant advancements to modern medicine. Full article
(This article belongs to the Special Issue Pre-Clinical Studies of Personalized Medicine for Cancer Research)
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Other

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16 pages, 1797 KiB  
Systematic Review
Fantastic Frogs and Where to Use Them: Unveiling the Hidden Cinobufagin’s Promise in Combating Lung Cancer Development and Progression Through a Systematic Review of Preclinical Evidence
by Sandra Maria Barbalho, Karina Torres Pomini, Enzo Pereira de Lima, Jéssica da Silva Camarinha Oliveira, Beatriz Leme Boaro, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Rose Eli Grassi Rici, Durvanei Augusto Maria, Jesselina Francisco dos Santos Haber, Virgínia Maria Cavallari Strozze Catharin, Patrícia Cincotto dos Santos Bueno, Eliana de Souza Bastos Mazuqueli Pereira, Ricardo de Alvares Goulart and Lucas Fornari Laurindo
Cancers 2024, 16(22), 3758; https://doi.org/10.3390/cancers16223758 - 7 Nov 2024
Cited by 1 | Viewed by 1189
Abstract
Cinobufagin (CB), a bufadienolide, has shown promising potential as an anticancer agent, particularly in combating lung cancer. This systematic review synthesizes preclinical evidence on CB’s effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. We analyzed data [...] Read more.
Cinobufagin (CB), a bufadienolide, has shown promising potential as an anticancer agent, particularly in combating lung cancer. This systematic review synthesizes preclinical evidence on CB’s effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. We analyzed data from various preclinical studies involving both in vitro cell line models and in vivo animal models. The reviewed studies indicate that CB effectively reduces cell viability, induces apoptosis, and inhibits cell proliferation, migration, and invasion across multiple lung cancer cell lines and xenograft models. Specifically, CB was found to decrease cell viability and increase apoptosis in lung cancer cells by modulating key molecular pathways, including Bcl-2, Bax, cleaved caspases, caveolin-1, FLOT2, Akt, STAT3, and FOXO1. In vivo studies further demonstrated significant inhibition of tumor growth with minimal toxicity. However, limitations include reliance on in vitro models, which may not fully represent in vivo tumor dynamics, and a lack of long-term safety data. The studies also vary in their methodologies and cell line models, which may not accurately encompass all lung cancer subtypes or predict human responses. Despite these limitations, CB’s ability to target specific molecular pathways and its promising results in preclinical models suggest it could be a valuable addition to lung cancer treatment strategies. Our review suggests further clinical trials to validate its efficacy and safety in humans. Future research should explore combination therapies and optimize delivery methods to enhance clinical outcomes. Full article
(This article belongs to the Special Issue Pre-Clinical Studies of Personalized Medicine for Cancer Research)
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