Invisible Player: Radiation from Cancer Risk to therapies

Invisible Player: Radiation from Cancer Risk to therapies

FIRST YEAR MEDTEC SCHOOL, A.A. 2025/2026

CELL BIOLOGY, HISTOLOGY AND EMBRIOLOGY COURSE

Types of Radiation:

1. Non-Ionising: Ex. ultraviolet (UV) light, microwaves, radio waves, and visible light 2. Ionising: a) Directly Ionising: Charged Particles - Alpha particles: low penetration, stopped by outer layers of skin - Beta particles: penetrate a few centimeters into tissue - Protons: finite, highly controllable range b) Indirectly Ionising: Neutral Particles/Photons - X-rays and Gamma rays: deep penetration capabilities

Dangers of Radiation: The Case of Clarence Dally

Who? Unshielded X-Ray Exposure -> Acute Radiation Dermatitis -> Squamous Cell Carcinoma -> Metastasis Why is it important?

IONIZING RADIATION

• X - Ray
• Single and double strand breaks of DNA and RNA
• Radiolysis of water and ROS
• Clustered lesions and oxidative base modifications (8-oxoG)
• DNA repair, apoptosis or malignant transformations

NON IONIZING RADIATION

• UV radiation
• Cyclobutane pyrimidine dimers (CPDs)
• Nucleotide excision repair (NER)
• C→T mutations and inherited defects in repair systems
• Eccessive exposure greatly increase skin cancer risk

We could have different effects in gene expression:

Mutations in p53 tumor suppressor pathway and p16 cell cycle regulation pathway,

Sonic Hedgehog signaling pathway in BCC, RAS oncogene activation

Release of immunosuppressive cytokines IL-10, TNF-α, and IL-1α.

Radiation-Induced Tumor Progression: A Histological Perspective

Lentigo maligna

RADIATION AND EMBRYONIC DEVELOPMENT

1.

RESISTANT PERIOD

2.

MAX. SUSCEPTABILITY PERIOD

3.

LOW SUSCEPTABILITY PERIOD

The developmental stages can be divided in:

25+

EFFECT OF RADIATIONS ON THE EMBRYO

STOCHASTIC

DETERMINISTIC

Stochastic effects are long term effects, resulting from damaged or incorrectly repaired DNA in a cell.

Deterministic effects are health effects caused from death or malfunction of a large population of cells

examples of deterministic effects are:

One main example of stochastic effect is the increase in childhood cancer

• Structural malformations

->anophtalamia->microphtalamia

• Loss of neural progenitors -> microcephaly

a medical paradox

The same physical agent capable of inducing carcinogenesis can also be used to treat cancer.

from radiation damage

to radiotherapy

DNA damage

Targeted irradiation

• Bragg peak
• high dose conformity
• reduced exit dose
• tissue sparing

DNA damage in cancer cells, especially vulnerable because of rapid proliferation, genomic instability and defective repair mechanisms

ROS production

uncontrolled exposure

controlled exposure

Mutations

Effects also on healthy tissue

Therapeutic ratio: maximize tumor control minimize normal tissue toxicity

Genomic instability

Carcinogenesis

Evolution of the Therapeutic Ratio

tumor control vs normal tissue toxicity

2) Electrons

1) Photons

• superficial lesions
• rapid dose fall-off
• tissue sparing
• penumbra

• deep tumors
• high versatility
• exit dose: healthy tissue

exposure

4) Protons

3) Brachytherapy

• Bragg peak
• high dose conformity
• reduced exit dose
• tissue sparing

Current challenges

• organ motion
• tissue variability
• range uncertainty
• biological uncertainty

• iridium-192 isotopes
• local dose escalation
• steep dose gradient
• cosmetic preservation

Interview with Enrico Pozzo, researcher and head of the Proton Centre in Humanitas

Humanitas Proton Building

• integrated proton center
• multidisciplinary oncology
• clinical trials
• advanced imaging

THANK YOU FOR YOUR ATTENTION!

HISTOLOGY: https://pmc.ncbi.nlm.nih.gov/articles/PMC2564815/ https://www.researchgate.net/figure/Comparison-of-melanoma-in-situ-lentigo-maligna-type-A-and-pigmented-actinic_fig5_51470771 TECH DROP: https://www.humanitas.it/news/proton-building-la-casa-delle-cure-oncologiche/ Salem PP, Chami P, Daou R, Hajj J, Lin H, Chhabra AM, Simone CB 2nd, Lee NY, Hajj C. Proton Radiation Therapy: A Systematic Review of Treatment-Related Side Effects and Toxicities. Int J Mol Sci. 2024 Oct 11;25(20):10969. doi: 10.3390/ijms252010969. PMID: 39456752; PMCID: PMC11506991. https://www.sciencedirect.com/science/article/pii/S1278321824001409?via%3Dihub

REFERENCES: EMBRIOLOGY: https://www.ncbi.nlm.nih.gov/books/NBK564358/ https://pubmed.ncbi.nlm.nih.gov/2643529/ CELL BIOLOGY: https://storage.imrpress.com/imr/journal/FBL/article/493471/1752770882342.pdf https://pmc.ncbi.nlm.nih.gov/articles/PMC8477449/#Sec6 https://www.sciencedirect.com/science/article/pii/S0160412024001211#s0015 https://genome.cshlp.org/content/13/9/2092 https://pmc.ncbi.nlm.nih.gov/articles/PMC4064600/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8477449/

Manasvita Basa, Ida Cassini, Simone Fumarola, Eleonora Reginelli, Samuele JunSeob Shin, Sara Valcarenghi

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