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Tumor Biobanks at the Service of Precision Medicine
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Tumor Biobanks at the Service of Precision Medicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 January 2021) | Viewed by 25342

Special Issue Editors

Dr. Monica Cantile

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Guest Editor
Pathology Unit, Istituto Nazionale Tumori-Irccs-Fondazione G. Pascale, 80131 Naples, Italy
Interests: tumor biomarkers; molecular pathology; tumor biobank; non coding RNAs; HOX genes; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Gerardo Botti

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Guest Editor
Pathology Unit-Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Naples, Italy
Interests: diagnostic pathology; tumor biomarkers; homeobox genes; non-coding RNAs; tumor microenvironment

Special Issue Information

Dear Colleagues,

Biobanks represent "service units" inside of public or private health facilities, with no direct profit making, aimed at collecting, storing, processing, and distributing human biological material. In recent years, among the disease-oriented biobanks, the tumor biobank has certainly collected the greatest interest and centralized most of the funding. Among the biomaterials types stored in the tumor biobanks, there are tumor tissues, healthy tissues, cells, nucleic acids, proteins, peripheral blood samples, and other body fluids (saliva, urine, etc.). The clinic, demographic, and molecular data from patients should be recorded in dedicated databases that can be consulted in compliance with the laws protecting privacy and the use of genetic data. The main purpose of the tumor biobank is to promote studies aimed at identifying pathogenetic and progression-inducing alterations, but also studying the correlations between specific gene profiles and lifestyles, environmental exposure, etc.

However, if originally, the biobanks were implemented exclusively to support translational research, today the scenario has completely changed. In the clinical–diagnostic field, it has become mandatory to guarantee the quality of biomaterials to identify predictive biomarkers of therapeutic response and to study the molecular mechanisms related to drug resistance. In the last 20 years, the introduction of -omics (genomics, transcriptomics, proteomics, metabolomics) in the characterization of tumor diseases has led to the identification of hundreds of potential biomarkers; however, very few have been validated with clinical studies on biological samples. Biobanks, providing biological samples and associated quality data, are therefore indispensable for enhancing precision medicine in clinical practice by promoting diagnostic pathways designed ad hoc for the patient, with a great impact on the overall health of the population.

This Special Issue will provide a comprehensive update on advances in precision medicine in oncology, highlighting the need to provide high-quality biomaterials, preserved according to standardized operating procedures within certified biobanks.

Prof. Monica Cantile
Prof. Gerardo Botti
Guest Editors

Manuscript Submission Information

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Keywords

  • pre-analytical procedures
  • ISO standard for general requirements in biobanking
  • tissue and biofluid treatment and storage
  • new biomarkers in cancer precision medicine
  • molecular pathways related to drug resistance mechanisms
  • circulating biomarkers usable for early diagnosis
  • biomarkers of “susceptibility” for predicting individual risk

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Published Papers (3 papers)

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Research

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20 pages, 7487 KiB  
Article
Hiltonol Cocktail Kills Lung Cancer Cells by Activating Cancer-Suppressors, PKR/OAS, and Restraining the Tumor Microenvironment
by Shu-Chun Chang, Bo-Xiang Zhang, Emily Chia-Yu Su, Wei-Ciao Wu, Tsung-Han Hsieh, Andres M. Salazar, Yen-Kuang Lin and Jeak Ling Ding
Int. J. Mol. Sci. 2021, 22(4), 1626; https://doi.org/10.3390/ijms22041626 - 5 Feb 2021
Cited by 13 | Viewed by 4284
Abstract
NSCLC (non-small cell lung cancer) is a leading cause of cancer-related deaths worldwide. Clinical trials showed that Hiltonol, a stable dsRNA representing an advanced form of polyI:C (polyinosinic-polycytidilic acid), is an adjuvant cancer-immunomodulator. However, its mechanisms of action and effect on lung cancer [...] Read more.
NSCLC (non-small cell lung cancer) is a leading cause of cancer-related deaths worldwide. Clinical trials showed that Hiltonol, a stable dsRNA representing an advanced form of polyI:C (polyinosinic-polycytidilic acid), is an adjuvant cancer-immunomodulator. However, its mechanisms of action and effect on lung cancer have not been explored pre-clinically. Here, we examined, for the first time, how a novel Hiltonol cocktail kills NSCLC cells. By retrospective analysis of NSCLC patient tissues obtained from the tumor biobank; pre-clinical studies with Hiltonol alone or Hiltonol+++ cocktail [Hiltonol+anti-IL6+AG490 (JAK2 inhibitor)+Stattic (STAT3 inhibitor)]; cytokine analysis; gene knockdown and gain/loss-of-function studies, we uncovered the mechanisms of action of Hiltonol+++. We demonstrated that Hiltonol+++ kills the cancer cells and suppresses the metastatic potential of NSCLC through: (i) upregulation of pro-apoptotic Caspase-9 and Caspase-3, (ii) induction of cytosolic cytochrome c, (iii) modulation of pro-inflammatory cytokines (GRO, MCP-1, IL-8, and IL-6) and anticancer IL-24 in NSCLC subtypes, and (iv) upregulation of tumor suppressors, PKR (protein kinase R) and OAS (2′5′ oligoadenylate synthetase). In silico analysis showed that Lys296 of PKR and Lys66 of OAS interact with Hiltonol. These Lys residues are purportedly involved in the catalytic/signaling activity of the tumor suppressors. Furthermore, knockdown of PKR/OAS abrogated the anticancer action of Hiltonol, provoking survival of cancer cells. Ex vivo analysis of NSCLC patient tissues corroborated that loss of PKR and OAS is associated with cancer advancement. Altogether, our findings unraveled the significance of studying tumor biobank tissues, which suggests PKR and OAS as precision oncological suppressor candidates to be targeted by this novel Hiltonol+++ cocktail which represents a prospective drug for development into a potent and tailored therapy for NSCLC subtypes. Full article
(This article belongs to the Special Issue Tumor Biobanks at the Service of Precision Medicine)
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Review

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15 pages, 1898 KiB  
Review
NTRK Fusions, from the Diagnostic Algorithm to Innovative Treatment in the Era of Precision Medicine
by Federica Zito Marino, Francesca Pagliuca, Andrea Ronchi, Immacolata Cozzolino, Marco Montella, Massimiliano Berretta, Maria Elena Errico, Vittoria Donofrio, Roberto Bianco and Renato Franco
Int. J. Mol. Sci. 2020, 21(10), 3718; https://doi.org/10.3390/ijms21103718 - 25 May 2020
Cited by 53 | Viewed by 8850
Abstract
In the era of precision medicine, the identification of several predictive biomarkers and the development of innovative therapies have dramatically increased the request of tests to identify specific targets on cytological or histological samples, revolutionizing the management of the tumoral biomaterials. The Food [...] Read more.
In the era of precision medicine, the identification of several predictive biomarkers and the development of innovative therapies have dramatically increased the request of tests to identify specific targets on cytological or histological samples, revolutionizing the management of the tumoral biomaterials. The Food and Drug Administration (FDA) has recently approved a selective neurotrophic tyrosine receptor kinase (NTRK) inhibitor, larotrectinib. Contemporarily, the development of multi-kinase inhibitors with activity in tumors carrying TRK fusions is ongoing. Chromosomal translocations involving the NTRK1, NTRK2, and NTRK3 genes result in constitutive activation and aberrant expression of TRK kinases in numerous cancer types. In this context, the identification of tumors harboring TRK fusions is crucial. Several methods of detection are currently available. We revise the advantages and disadvantages of different techniques used for identifying TRK alterations, including immunohistochemistry, fluorescence in situ hybridization, reverse transcriptase polymerase chain reaction, and next generation sequencing-based approaches. Finally, we propose a diagnostic algorithm based on histology and the relative frequency of TRK fusions in each specific tumor, considering also the economic feasibility in the clinical practice. Full article
(This article belongs to the Special Issue Tumor Biobanks at the Service of Precision Medicine)
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18 pages, 3588 KiB  
Review
Human Ovarian Cortex biobanking: A Fascinating Resource for Fertility Preservation in Cancer
by Erica Silvestris, Giuseppe De Palma, Stefano Canosa, Simone Palini, Miriam Dellino, Alberto Revelli and Angelo Virgilio Paradiso
Int. J. Mol. Sci. 2020, 21(9), 3245; https://doi.org/10.3390/ijms21093245 - 4 May 2020
Cited by 19 | Viewed by 11326
Abstract
Novel anti-cancer treatments have improved the survival rates of female young patients, reopening pregnancy issues for female cancer survivors affected by the tumor treatment-related infertility. This condition occurs in approximately one third of women of fertile age and is mainly dependent on gonadotoxic [...] Read more.
Novel anti-cancer treatments have improved the survival rates of female young patients, reopening pregnancy issues for female cancer survivors affected by the tumor treatment-related infertility. This condition occurs in approximately one third of women of fertile age and is mainly dependent on gonadotoxic protocols, including radiation treatments. Besides routine procedures such as the hormonal induction of follicular growth and subsequent cryopreservation of oocytes or embryos, the ovarian protection by gonadotropin-releasing hormone (GnRH) agonists during chemotherapy as well as even gonadal shielding during radiotherapy, other innovative techniques are available today and need to be optimized to support their introduction into the clinical practice. These novel methods are hormone stimulation-free and include the ovarian cortex cryopreservation before anti-cancer treatments and its subsequent autologous reimplantation and a regenerative medicine approach using oocytes derived in vitro from ovarian stem cells (OSCs). For both procedures, the major benefit is related to the prompt recruitment and processing of the ovarian cortex fragments before gonadotoxic treatments. However, while the functional competence of oocytes within the cryopreserved cortex is not assessable, the in vitro maturation of OSCs to oocytes, allows to select the most competent eggs to be cryopreserved for fertility restoration. Full article
(This article belongs to the Special Issue Tumor Biobanks at the Service of Precision Medicine)
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