The following is excerpted from a WebEx that EpicentRx gave in January.
“Divert shields!” is a common battle cry from the captain of the USS Enterprise in the TV show/movie Star Trek when one part the spaceship is under “phaser” or ray attack, which if you’ve ever watched it, is almost always.
Shields refers to a “force field” or “energy field” that protects fixed parts or quadrants of the spaceship from weapons fire like “phasers” or “photon torpedoes” and is moveable or divertible depending on the angle of attack.
The problem with moving the shield force field from one area of the ship, say the right side, to the left side if the left side is taking fire is that now the right side of the ship is exposed and therefore, vulnerable.
However, according to the Law of Conservation of Energy, which is adhered to even in science fiction, power reserves are finite and hence, rather than covering the whole ship, the shield must be employed and re-directed to select areas where it is most needed.
It’s the same with cancer cells. Energy or ATP (the currency of the cancer cell) reserves are not infinite and therefore, must be diverted, re-routed or re-allocated depending on the dominant form of attack for maximal protection and resistance.
If that attack is in the form of chemotherapy, then the cancer cell must upregulate its drug efflux pumps, for example, possibly to the detriment of other defense mechanisms.
If the attack is now changed to or includes cytotoxic T cells, then the cancer cell must react to and expend more energy on immune evasion through immune checkpoint upregulation, for example – again possibly to the detriment of other activities, which in theory makes the cancer cell vulnerable to another form of attack.
In other words, the resistance “shell game” moves or develops in response to one selective pressure, say chemotherapy or checkpoint inhibition, which has the potential to make the tumor cell vulnerable to another form of attack.
The standard paradigm in oncology is not to retreat with the same therapy after disease progression on the assumption that resistance has developed, and that resistance is stable, and homogeneous, so retreatment would only expose patients to toxicity minus the benefit.
However, the introduction of sensitizing therapies like AdAPT-001 and RRx-001 may encourage a paradigm switch from “one and done” to “one and not done” along the lines of if at first you don’t succeed with one therapy try, try again. Such a paradigm shift, if successful, would buy patients, especially metastatic patients, more of what they so desperately want and need which is, of course, time.