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π Health and biotech
Tumours: “better understanding has improved treatments”

Advances in physics: “new radiotherapies are on the horizon”

Alessandro Flacco, Associate professor at ENSTA (IP Paris)
On October 21st, 2021 |
3 mins reading time
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Advances in physics: “new radiotherapies are on the horizon”
Alessandro Flacco
Alessandro Flacco
Associate professor at ENSTA (IP Paris)
Key takeaways
  • Radiotherapy is used to destroy cancer cells as precisely as possible, without affecting the surrounding healthy cells.
  • Since the 1990s, doctors have been using proton therapies, and more recently, the use of electron beams in cancer treatment has been studied.
  • Recent findings showed that the toxicity of radiation is related to the duration of exposure; known as the ‘flash effect’, a short burst of radiation.
  • The shorter the time, the less healthy cells are affected thanks to less burning and less fibrosis.
  • This discovery has prompted scientists to re-explore sources of particles such as pulsed lasers that provide fast and very locally intense radiation – or by injecting nanoparticles.

Con­trary to what we may think, it is not only bio­log­i­cal sci­ence research that con­tributes to advances in can­cer ther­a­py. Physics, and in par­tic­u­lar par­ti­cle sci­ence, has also con­tributed to impor­tant ther­a­peu­tic advances; par­tic­u­lar­ly involved in both improve­ments in effec­tive­ness and reduc­tions in side effects of radio­ther­a­py, which accounts for more than half of all treatments. 

Eliminating tumours

To under­stand this progress, we must first under­stand the prin­ci­ple of radio­ther­a­py; an approach that con­sists of elim­i­nat­ing can­cer cells using radi­a­tion. This radi­a­tion destroys the can­cer cells as pre­cise­ly as pos­si­ble, with­out affect­ing the sur­round­ing healthy cells. To achieve this, doc­tors rely on radi­a­tion-induced tox­i­c­i­ty, i.e. the low­er resis­tance of can­cer cells to the effects of radi­a­tion com­pared to nor­mal cells. This prop­er­ty ensures the ther­a­peu­tic mar­gin, the dif­fer­ence between an effec­tive dose* and a tox­ic dose. The lat­ter is also the result of topo­log­i­cal advances and bet­ter beam focus­ing. The com­bi­na­tion of these two phe­nom­e­na, radi­a­tion-induced tox­i­c­i­ty and topol­o­gy, pro­tects the healthy tis­sue around the tumour.

Ion­is­ing rays deposit ener­gy deep in the tis­sue. They act at dif­fer­ent lev­els: atom­ic, mol­e­c­u­lar, chem­i­cal, bio­log­i­cal, and phys­i­o­log­i­cal. At the atom­ic lev­el, radi­a­tion inter­acts with the chem­i­cal com­po­nents con­tained with­in cells. Their ion­is­ing actions pro­duce reac­tive species, such as free rad­i­cals, which can also destroy DNA and dri­ve the cell to death. They also act direct­ly at the mol­e­c­u­lar lev­el, pro­duc­ing breaks in the DNA mol­e­cules. If there is enough dam­age, it over­whelms the cell’s self-repair process­es. So, when the cell attempts to divide, as can­cer cells do, it fails to com­plete its divi­sion and dies. This amount of dam­age attacks the struc­ture of the tumour.

Sev­er­al types of par­ti­cles can be used: X‑rays (pho­tons) are the most com­mon. Since the 1990s, doc­tors have been using pro­ton ther­a­pies, and more recent­ly, the use of elec­tron beams in can­cer treat­ment has been studied.

Finding the right dose

The mech­a­nisms of how radio­ther­a­py works are known, and its bio­log­i­cal con­trol seemed clear. And it was thought that the bio­log­i­cal effect was induced by the dose of radi­a­tion admin­is­tered, a dose-response effect typ­i­cal of biol­o­gy. But recent­ly this cer­tain­ty has been over­turned as it was dis­cov­ered that the time pro­file of the dose alters the tox­i­c­i­ty of the radi­a­tion1. This is known as the ‘flash effect’, which con­sists of deliv­er­ing the dose of radi­a­tion in an extreme­ly short time – over a few mil­lisec­onds instead of sev­er­al minutes.

The short­er the time, the low­er the sen­si­tiv­i­ty of healthy cells to the radi­a­tion, while that of can­cer cells remains the same. The Flash effect thus increas­es the ther­a­peu­tic mar­gin. In prac­tice, this reduces the unde­sir­able effects of radio­ther­a­py by caus­ing less burn­ing and pro­duc­ing less fibro­sis – abnor­mal scar­ring of healthy tis­sue that can hin­der the func­tion­ing of an organ, such as the liv­er or lungs when they are close to the irra­di­at­ed area.

This effect is increas­ing­ly doc­u­ment­ed by clin­i­cal research, but the pre­cise expla­na­tion is still miss­ing, open­ing up a new field of research. 

New lasers

This dis­cov­ery has prompt­ed sci­en­tists to re-explore sources of par­ti­cles. In this respect, my team and I are study­ing the val­ue of laser radi­a­tion. Unlike con­ven­tion­al sys­tems, lasers are pulsed rather than con­tin­u­ous sources of par­ti­cles. Laser sources have a dif­fer­ent time pro­file to con­ven­tion­al or even Flash sources. The radi­a­tion gen­er­at­ed is both very fast and very local­ly intense. We are cur­rent­ly try­ing to study its bio­log­i­cal effect and it does not seem to be com­pa­ra­ble to the Flash effect.

On cells in cul­ture, we have observed a bio­log­i­cal effect, a tox­i­c­i­ty of can­cer cells which seems inter­est­ing2. We are cur­rent­ly study­ing the fea­si­bil­i­ty of car­ry­ing out in vivo tests to bet­ter con­firm this effect. Oth­er progress is linked to advances in physics. This is the case with nanopar­ti­cles, which aim to con­cen­trate irra­di­a­tion local­ly. The idea is to inject these nanopar­ti­cles into the tumour. They poten­ti­ate the radi­a­tion and thus make it pos­si­ble to admin­is­ter a low­er lev­el of irra­di­a­tion for a con­stant bio­log­i­cal effect. This reduces the side effects, too.

Oth­er nanopar­ti­cles release drugs when irra­di­at­ed. They form an inert cage that traps cyto­tox­ic mol­e­cules. Under the local action of radi­a­tion, the cage opens and releas­es the anti-can­cer treat­ment. This approach is designed to pre­vent the patient from being sub­ject­ed to gen­er­al drug tox­i­c­i­ty. Only the irra­di­at­ed area is in con­tact with the cyto­tox­ic molecules.

And that’s just to men­tion ther­a­peu­tic progress because diag­no­sis, with the major progress made in can­cer imag­ing, is anoth­er area that is fed by progress in the phys­i­cal sciences.

* dose: the ener­gy deposit­ed on a mass of tissue

Interview by Agnes Vernet
1Favaudon et al. Sci­ence Transl Med 2014  doi : 10.1126/scitranslmed.3008973 https://​www​.sci​ence​.org/​d​o​i​/​1​0​.​1​1​2​6​/​s​c​i​t​r​a​n​s​l​m​e​d​.​3​0​08973
2Bayart et al. Sci­en­tif­ic Reports 2019 https://doi.org/10.1038/s41598-019–46512‑1

Contributors

Alessandro Flacco

Alessandro Flacco

Associate professor at ENSTA (IP Paris)

Alessandro Flacco works on the application of laser particle sources to biology and medicine. He has long worked on the physics of plasmas created by very high intensity lasers and on the acceleration of protons by laser-matter interaction. He is an associate professor at ENSTA Paris and a researcher at LOA (Laboratoire d'Optique Appliquée: joint research unit CNRS, ENSTA, École Polytechnique).