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

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. 

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.

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. 

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