Special Issue "Advances in Personalized Treatment of Cancer (Powered By: 4oncommunity)"

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Methodology, Drug and Device Discovery".

Deadline for manuscript submissions: 20 July 2023 | Viewed by 16371

Special Issue Editors

1. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
2. Division of Pathology, IRCCS European Institute of Oncology (IEO), Milan, Italy
Interests: translational research; breast cancer; biomarkers; immunology; molecular pathology; TILs; precision medicine
Special Issues, Collections and Topics in MDPI journals
New Drugs and Early Drug Development for Innovative Therapies Division, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
Interests: breast cancer; new drugs; clinical trials; translational research; immunotherapy
Special Issues, Collections and Topics in MDPI journals
Department of Medicine, University of Verona, P.le L.A. Scuro 10, 37134 Verona, Italy
Interests: lung cancer; translational research; chemotherapy; targeted therapy; immunotherapy; methodology of clinical trials; nutrition; physical activity and psychological aspects of cancer patients

Special Issue Information

Dear Colleagues, 

We are experiencing an amazing era of advances in the diagnosis and treatment of cancer. In this evolving scenario, predictive molecular pathology is called to face new challenges. Our increased diagnostic resolution, coupled with the integration of clinicopathologic information, and big molecular data, is allowing for a growth in the selective capacity of molecular targeted treatments. Novel biomarkers at genomic, transcriptomic, proteomic, and immunologic levels have been discovered, and more accurate testing methods and guidelines are expected. These biomarkers are strongly impacting treatment decision making in patients with cancer.

4oncommunity is a platform that systematizes the growing amount of information regarding precision medicine, but also a virtual space in which to share experiences and knowledge for the advancement of the oncology community.

This Special Issue is edited by the Scientific Board of 4oncommunity (www.4oncommunity.com Twitter: @4oncommunity) to provide a comprehensive portrait of the current state of knowledge of biomarkers for the clinical management of cancer patients. One of the aims of this initiative is to foster a novel approach in collaborating between scientists working on cancer. We especially welcome review articles (either systematic or discursive), original translational research studies, and short communications.

Prof. Dr. Matteo Fassan
Dr. Umberto Malapelle
Prof. Dr. Nicola Fusco
Prof. Dr. Fabio Pagni
Dr. Carmen Criscitiello
Dr. Sara Pilotto
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 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. Journal of Personalized Medicine 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 2000 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

  • cancer
  • biomarkers
  • precision medicine
  • pathology
  • molecular pathology
  • oncology

Published Papers (8 papers)

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Research

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Article
PIK3CAMutations in Breast Cancer Subtypes Other Than HR-Positive/HER2-Negative
J. Pers. Med. 2022, 12(11), 1793; https://doi.org/10.3390/jpm12111793 - 31 Oct 2022
Viewed by 1480
Abstract
The phosphoinositide 3-kinase (PI3K) pathway plays a key role in cancer, influencing growth, proliferation, and survival of tumor cells. PIK3CA mutations are generally oncogenic and responsible for uncontrolled cellular growth. PI3K inhibitors (PI3Ki) can inhibit the PI3K/AKT/mTOR pathway, although burdened by not easily [...] Read more.
The phosphoinositide 3-kinase (PI3K) pathway plays a key role in cancer, influencing growth, proliferation, and survival of tumor cells. PIK3CA mutations are generally oncogenic and responsible for uncontrolled cellular growth. PI3K inhibitors (PI3Ki) can inhibit the PI3K/AKT/mTOR pathway, although burdened by not easily manageable toxicity. Among PI3Ki, alpelisib, a selective p110α inhibitor, is approved for the treatment of hormone receptor (HR)+/HER2- PIK3CA mutant metastatic breast cancer (BC) that has progressed to a first line endocrine therapy. PIK3CA mutations are also present in triple negative BC (TNBC) and HER2+ BC, although the role of PI3K inhibition is not well established in these subtypes. In this review, we go through the PI3K/AKT/mTOR pathway, describing most common mutations found in PI3K genes and how they can be detected. We describe the available biological and clinical evidence of PIK3CA mutations in breast cancers other than HR+/HER2-, summarizing clinical trials investigating PI3Ki in these subtypes. Full article
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Article
Survival Impact of Long-Term Tramadol Use on Breast Cancer for Patients with Chronic Pain: A Propensity Score-Matched Population-Based Cohort Study
J. Pers. Med. 2022, 12(3), 384; https://doi.org/10.3390/jpm12030384 - 02 Mar 2022
Viewed by 1913
Abstract
Purpose: The impact of tramadol analgesic use before breast cancer diagnosis on survival in patients with chronic pain is unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare the breast cancer-related survival of patients with chronic pain who received long-term [...] Read more.
Purpose: The impact of tramadol analgesic use before breast cancer diagnosis on survival in patients with chronic pain is unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare the breast cancer-related survival of patients with chronic pain who received long-term tramadol analgesic treatment with that of those who did not receive such treatment. Patients and Methods: We included patients with chronic pain and categorized them into two groups according to their analgesic use, comparing their breast cancer-related survival; patients with breast cancer and chronic pain who were prescribed ≥180 defined daily doses (DDDs) of tramadol analgesics per year >3 months before breast cancer diagnosis comprised the case group, and those who were prescribed non-tramadol analgesics before breast cancer diagnosis comprised the control group. Patients in both groups were matched at a ratio of 1:5. Results: The matching process yielded a final cohort of 624 patients (104 and 520 in the case and control groups, respectively) who were eligible for further analysis. According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratio for all-cause death in the case group compared with in the control group was 3.45 (95% confidence interval = 2.36–5.04; p < 0.001). Conclusion: Long-term tramadol analgesic use prior to breast cancer diagnosis might be associated with poor overall survival in patients with chronic pain compared with such patients that did not receive long-term tramadol analgesic treatment. Full article
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Article
Physical Exercise with or without Whole-Body Vibration in Breast Cancer Patients Suffering from Aromatase Inhibitor—Induced Musculoskeletal Symptoms: A Pilot Randomized Clinical Study
J. Pers. Med. 2021, 11(12), 1369; https://doi.org/10.3390/jpm11121369 - 14 Dec 2021
Cited by 7 | Viewed by 2295
Abstract
In this study, we aimed to assess the safety and efficacy of physical exercise, with or without whole-body vibration (WBV), in patients with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS). Eligible patients were adults (≥18 years) with a history of breast cancer and current AIMSS. [...] Read more.
In this study, we aimed to assess the safety and efficacy of physical exercise, with or without whole-body vibration (WBV), in patients with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS). Eligible patients were adults (≥18 years) with a history of breast cancer and current AIMSS. Enrolled patients (n = 22) were randomly assigned 1:1 to receive physical exercise combined with WBV or sham WBV for 4 weeks. The primary endpoint was pain intensity measured by numerical pain rating scale (NPRS). The secondary endpoints were muscle strength, physical function, physical performance, and quality of life. The WBV group (mean age: 51.73 ± 10.73 years; body mass index (BMI): 25.56 ± 5.17 kg/m2) showed a statistically significant pain reduction (NPRS: 6.82 ± 1.17 vs. 5.73 ± 1.01; p = 0.031), whereas patients in the sham WBV group (mean age: 58.55 ± 9.71 years; BMI: 27.31 ± 3.84 kg/m2), did not reach statistical significance (NPRS: 6.91 ± 2.02 vs. 5.91 ± 2.51; p = 0.07). Concurrently, muscle strength, physical performance, and quality of life significantly improved in both groups, without significant differences between groups. No dropouts and no side effects were recorded. Both patients and the physical therapist reported a high level of satisfaction with the intervention. Our findings suggest that physical exercise and WBV combination might be a safe therapeutic option for improving the rehabilitative management of patients with AIMSS. Full article
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Article
Pre-Treatment Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Occult Cervical Metastasis in Clinically Negative Neck Supraglottic and Glottic Cancer
J. Pers. Med. 2021, 11(12), 1252; https://doi.org/10.3390/jpm11121252 - 25 Nov 2021
Cited by 1 | Viewed by 1204
Abstract
Background. Among patients with diagnosis of Laryngeal Squamous Cell Carcinoma (LSCC), up to 37.5% of cases may have occult metastasis (OM), and this feature is linked to poor prognosis and high rate of local recurrence. The role of elective neck dissection (END) in [...] Read more.
Background. Among patients with diagnosis of Laryngeal Squamous Cell Carcinoma (LSCC), up to 37.5% of cases may have occult metastasis (OM), and this feature is linked to poor prognosis and high rate of local recurrence. The role of elective neck dissection (END) in clinically negative neck (cN0) LSCC remains controversial. It is of great value to search for low-cost and easily detectable indicators to predict the risk of OM in laryngeal cancer. Recent reports have shown that high values of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) represent a negative prognostic factor in head and neck cancers. The aim of our study has been to investigate the value of pre-treatment NLR and PLR with regard to predicting occult cervical metastasis in cN0 supraglottic and glottic LSCC. Materials and methods. Data of patients affected by LSCC, who had been surgically treated by means of laryngectomy (total, horizontal partial and supracricoid) and END between January 2006 and January 2021, were retrospectively reviewed, using information retrieved from a database dedicated to such procedures in a single tertiary care referral institute. Results. A total of 387 patients were treated for LSCC at our Institute from 2006 to 2021, but only 108 of them met the inclusion criteria. The median age at the time of diagnosis was 64 years (range, 39–89 years). All the tumors were treated with a laryngectomy and an END. A total of 27.7% of patients were found positive for neck node metastasis (the pN+ group), while 78/108 (72.3%) patients were found to be negative for the presence of neck metastasis (the pN0 group). High values of NLR, but not PLR, significantly correlated with the probability of OM, and according to the iterative algorithm of Newton–Raphson, an NLR value of 2.26 corresponds to a probability of OM of 20%. Conclusion. Our analysis revealed a statistical correlation between high NLR pre-treatment values and positive neck OM in patients with LSCC. Full article
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Review

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Review
Effect of Radio-Chemotherapy on PD-L1 Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma
J. Pers. Med. 2023, 13(2), 363; https://doi.org/10.3390/jpm13020363 - 18 Feb 2023
Viewed by 968
Abstract
Background: Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. Methods: [...] Read more.
Background: Programmed death-ligand 1 (PD-L1) checkpoint inhibitors represent a mainstay of therapy in head and neck squamous cell cancer (HNSCC). However, little is known about the influence of combined therapy on PD-L1 expression. The study aims to gather evidence on this topic. Methods: A systematic search was carried out in electronic databases Pubmed-MEDLINE and Embase to retrieve studies on the comparison of PD-L1 expression before and after conventional therapy. Data were extracted and a quantitative analysis with pooled odds ratios (ORs) was performed when applicable. Results: Of 5688 items, 15 were finally included. Only a minority of studies assessed PD-L1 with the recommended combined positive score (CPS). The results are highly heterogeneous, with some studies reporting an increase in PD-L1 expression and others reporting a decrease. Three studies allowed for quantitative analysis and showed a pooled OR of 0.49 (CI 0.27–0.90). Conclusions: From the present evidence, a clear conclusion towards an increase or decrease in PD-L1 expression after combined therapy cannot be drawn, but even with few studies available, a trend towards an increase in expression in tumor cells at a cutoff of 1% can be noted in patients undergoing platinum-based therapy. Future studies will provide more robust data on the effect of combined therapy on PD-L1 expression. Full article
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Review
Homologous Recombination Deficiency in Ovarian Cancer: from the Biological Rationale to Current Diagnostic Approaches
J. Pers. Med. 2023, 13(2), 284; https://doi.org/10.3390/jpm13020284 - 02 Feb 2023
Cited by 1 | Viewed by 1344
Abstract
The inability to efficiently repair DNA double-strand breaks using the homologous recombination repair pathway is defined as homologous recombination deficiency (HRD). This molecular phenotype represents a positive predictive biomarker for the clinical use of poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors and platinum-based chemotherapy [...] Read more.
The inability to efficiently repair DNA double-strand breaks using the homologous recombination repair pathway is defined as homologous recombination deficiency (HRD). This molecular phenotype represents a positive predictive biomarker for the clinical use of poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors and platinum-based chemotherapy in ovarian cancers. However, HRD is a complex genomic signature, and different methods of analysis have been developed to introduce HRD testing in the clinical setting. This review describes the technical aspects and challenges related to HRD testing in ovarian cancer and outlines the potential pitfalls and challenges that can be encountered in HRD diagnostics. Full article
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Review
Atlas of PD-L1 for Pathologists: Indications, Scores, Diagnostic Platforms and Reporting Systems
J. Pers. Med. 2022, 12(7), 1073; https://doi.org/10.3390/jpm12071073 - 29 Jun 2022
Cited by 18 | Viewed by 2896
Abstract
Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering [...] Read more.
Background. Innovative drugs targeting the PD1/PD-L1 axis have opened promising scenarios in modern cancer therapy. Plenty of assays and scoring systems have been developed for the evaluation of PD-L1 immunohistochemical expression, so far considered the most reliable therapeutic predictive marker. Methods. By gathering the opinion of acknowledged experts in dedicated fields of pathology, we sought to update the currently available evidence on PD-L1 assessment in various types of tumors. Results. Robust data were progressively collected for several anatomic districts and leading international agencies to approve specific protocols: among these, TPS with 22C3, SP142 and SP263 clones in lung cancer; IC with SP142 antibody in breast, lung and urothelial tumors; and CPS with 22C3/SP263 assays in head and neck and urothelial carcinomas. On the other hand, for other malignancies, such as gastroenteric neoplasms, immunotherapy has been only recently introduced, often for particular histotypes, so specific guidelines are still lacking. Conclusions. PD-L1 immunohistochemical scoring is currently the basis for allowing many cancer patients to receive properly targeted therapies. While protocols supported by proven data are already available for many tumors, dedicated studies and clinical trials focusing on harmonization of the topic in other still only partially explored fields are surely yet advisable. Full article
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Review
FFPE-Based NGS Approaches into Clinical Practice: The Limits of Glory from a Pathologist Viewpoint
J. Pers. Med. 2022, 12(5), 750; https://doi.org/10.3390/jpm12050750 - 05 May 2022
Cited by 5 | Viewed by 2831
Abstract
The introduction of next-generation sequencing (NGS) in the molecular diagnostic armamentarium is deeply changing pathology practice and laboratory frameworks. NGS allows for the comprehensive molecular characterization of neoplasms, in order to provide the best treatment to oncologic patients. On the other hand, NGS [...] Read more.
The introduction of next-generation sequencing (NGS) in the molecular diagnostic armamentarium is deeply changing pathology practice and laboratory frameworks. NGS allows for the comprehensive molecular characterization of neoplasms, in order to provide the best treatment to oncologic patients. On the other hand, NGS raises technical issues and poses several challenges in terms of education, infrastructures and costs. The aim of this review is to give an overview of the main NGS sequencing platforms that can be used in current molecular diagnostics and gain insights into the clinical applications of NGS in precision oncology. Hence, we also focus on the preanalytical, analytical and interpretative issues raised by the incorporation of NGS in routine pathology diagnostics. Full article
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