A limitation of many pharmaceutical and biological therapies is the non-selective nature by which anti-cancer agents are administered to a patient. The vast majority of such externally-applied molecules can pass through cell membranes. Because of this, they will enter all cells and thus have no selectivity for affecting only cancer cells. Professor Binshtok and his team developed novel means for delivering anticancer compounds selectively into tumor cells. They have done it by exploiting the proteins that these cells selectively express, thus increasing the effectiveness of anticancer drugs and dramatically reducing their side effects. Professor Binshtok based this idea on the method he recently developed for the targeted delivery of charged, and therefore membrane impermeable, molecules selectively to pain neurons, thus producing for the first time selective pain blockade. He demonstrated that the activation of protein that is expressed only by pain-generating cells namely TRPV1 receptor, which senses harmful heat, produces a pore in the cell membrane which is large enough to allow for an electrically charged form of lidocaine (commonly used anesthetic), called QX-314, to penetrate selectively into pain neurons. Thus, QX-314, which is ineffective when injected into the tissue, enters only pain neurons and thereby blocks their activity without affecting neighboring motor and sensory cells. In the new paper Professor Binshtok utilizes similar proteins that are selectively expressed by tumor cells. He demonstrated that indeed, we are able to selectively target electrically charged chemotherapy agents Doxorubicin into liver tumor cells via the pore of TRPV2 receptor, a protein similar to TRPV1, which these cells selectively express. Moreover, the team showed that in the doses in which Doxorubicin has no effect whatsoever on cell vitality, when it is co-applied together with the agent that activates TRPV2 it leads to death of cancer cells. These results are very promising as they indicate that it might be very possible to use very low doses of chemotherapy (which by itself has neither side effects nor any potential therapeutic effect) together with an activator of the TRPV2, which will then reduce tumor size, maybe to the point of ablation. This would indicate that the platform increases the therapeutic index significantly, concomitant with a significant reduction in adverse effects.
This platform is promising in that it might give hope to patients with cancers which to date are non-treatable or the toxicity burden is unbearable.