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Radiotherapy and New Biological Paradigms in Cancer Treatments (2nd Edition)

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

Deadline for manuscript submissions: closed (15 May 2025) | Viewed by 2554

Special Issue Editor


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Guest Editor
Department of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, Verona, Italy
Interests: combination of immune checkpoint inhibitors and radiotherapy; radiation oncology and immunity; radiation oncology; immunotherapy; inflammation
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Special Issue Information

Dear Colleagues,

This collection is the second edition of "Radiotherapy and New Biological Paradigms in Cancer Treatments" (Radiotherapy is an important modality used in the treatment of more than 50% of cancer patients. However, despite sophisticated techniques for radiation delivery, as well as the combination of radiation with chemotherapy, tumors can recur.

In a cancer cell-centric view, radiotherapy is used against tumors because it determines cell injury and, thus, cell death. The central dogma of traditional radiobiology states that the cytotoxic effects of radiation on tumor cells are primarily due to the production of DNA double-strand breaks followed by some form of cell death, including apoptosis, necrosis, autophagy, mitotic catastrophe, or replicative senescence. In accordance, DNA damage and subsequent tumor cell death have been ascribed to four basic principles (known as the 4 “Rs” of radiobiology), i.e., reassortment of tumor cells into radiosensitive phases of the cell cycle (G2/M), reoxygenation of hypoxic areas within a tumor, repair of sublethal DNA damage, and repopulation of surviving tumor cells, whereby the manipulation of each factor alters tumor cell radiosensitivity.

Against this background, there is an abscopal effect (defined as “an action at a distance from the irradiated volume but within the same organism”) that it is not explainable within the aforementioned traditional radiotherapy view.  

Nowadays, there is more information about cancer and, above all, the interaction between the tumor and the host is considered essential on all sides. Tumor cells must interact with the host microenvironment and avoid immune destruction.

However, in most patients, radiation therapy can convert the tumor into an “in situ vaccine” able to induce a de novo anticancer immune response. The radiation-induced cell death is followed by the release of tumor antigens together with pro-inflammatory signals. First, it was demonstrated that cell death is an efficient process to transfer antigens from tumor cells to dendritic cells, which, in turn, are required to activate tumor-specific T cells. Moreover, in recent years, a functional redefinition of cell death, based on its effects on immune cells (i.e., tolerance or activation), has emerged as the “immunogenic cell death”.

This Special Issue will highlight the current state of the art in the immunostimulatory activity of radiotherapy, its role in tumor microenvironment, and its new paradigm of action.

Dr. Francesco Fiorica
Guest Editor

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Keywords

  • radiobiology
  • immunity
  • immunogenic cell death
  • cancer therapy

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Published Papers (2 papers)

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Review

18 pages, 1231 KiB  
Review
Narrative Review: Predictive Biomarkers of Tumor Response to Neoadjuvant Radiotherapy or Total Neoadjuvant Therapy of Locally Advanced Rectal Cancer Patients
by Joao Victor Machado Carvalho, Jeremy Meyer, Frederic Ris, André Durham, Aurélie Bornand, Alexis Ricoeur, Claudia Corrò and Thibaud Koessler
Cancers 2025, 17(13), 2229; https://doi.org/10.3390/cancers17132229 - 3 Jul 2025
Viewed by 563
Abstract
Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely [...] Read more.
Background/Objectives: Treatment of locally advanced rectal cancer (LARC) very often requires a neoadjuvant multimodal approach. Neoadjuvant treatment (NAT) encompasses treatments like chemoradiotherapy (CRT), short-course radiotherapy (SCRT), radiotherapy (RT) or a combination of either of these two with additional induction or consolidation chemotherapy, namely total neoadjuvant treatment (TNT). In case of complete radiological and clinical response, the non-operative watch-and-wait strategy can be adopted in selected patients. This strategy is impacted by a regrowth rate of approximately 30%. Predicting biomarkers of tumor response to NAT could improve guidance of clinicians during clinical decision making, improving treatment outcomes and decreasing unnecessary treatment exposure. To this day, there is no validated biomarker to predict tumor response to any NAT strategies in clinical use. Most research focused on CRT neglects the study of other regimens. Methods: We conducted a narrative literature review which aimed at summarizing the status of biomarkers predicting tumor response to NAT other than CRT in LARC. Results: Two hundred and fourteen articles were identified. After screening, twenty-one full-text articles were included. Statistically significant markers associated with improved tumor response pre-treatment were as follows: low circulating CEA levels; BCL-2 expression; high cellular expression of Ku70, MIB-1(Ki-67) and EGFR; low cellular expression of VEGF, hPEBP4 and nuclear β-catenin; the absence of TP53, SMAD4, KRAS and LRP1B mutations; the presence of the G-allel of LCS-6; and MRI features such as the conventional biexponential fitting pseudodiffusion (Dp) mean value and standard deviation (SD), the variable projection Dp mean value and lymph node characteristics (short axis, smooth contour, homogeneity and Zhang et al. radiomic score). In the interval post-treatment and before surgery, significant markers were as follows: a reduction in the median value of circulating free DNA, higher presence of monocytic myeloid-derived suppressor cells, lower presence of CTLA4+ or PD1+ regulatory T cells and standardized index of shape changes on MRI. Conclusions: Responders to neoadjuvant SCRT and RT tended to have a tumor microenvironment with an immune–active phenotype, whereas responders to TNT tended to have a less active tumor profile. Although some biomarkers hold great promise, scarce publications, inconsistent results, low statistical power, and low reproducibility prevent them from reliably predicting tumor response following NAT. Full article
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15 pages, 848 KiB  
Review
Metabolic-Modulating Effects of Radiation: Undetectable Yet Deadly—A Review on Radiotherapy
by Francesco Fiorica, Umberto Tebano, Giuseppe Napoli, Antonella Franceschetto, Marco Muraro, Carlotta Giorgi and Paolo Pinton
Cancers 2025, 17(1), 54; https://doi.org/10.3390/cancers17010054 - 27 Dec 2024
Cited by 1 | Viewed by 1245
Abstract
From a cancer-centric perspective, radiotherapy has been primarily viewed as a localised treatment modality, targeting cancer tissues with ionising radiation to induce DNA damage and cell death [...] Full article
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