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The phenomenon of cross-talk defines an escape mechanism whereby cancer cells blocked from one passage, find a second. When therapists have the capacity to block more than one pathway, the cancer cell is trapped and often dies. This is what's observed with duel inhibitor combinations.
With Perjeta (pertuzumab), this novel monoclonal antibody functions by preventing dimerization of HER-2 with the other members of the human epidermal growth factor family HER-1, HER-3 and HER-4. In so doing, the cross-talk between receptors is abrogated and downstream signaling is squelched.
Researchers had discovered that several small-molecule inhibitors of HER family kinases have shown limited efficacy in HER-2-driven breast cancers, despite effective inhibition of kinase activity. It is the failure to completely inhibit the kinase activity of HER-2 that allows oncogenic signaling through the kinase-inactive family members HER-1, HER-3 and HER-4 to continue.
When tested as a single agent early in its development, Perjeta showed only modest antitumor activity, however, it demonstrated synergy when used with Herceptin (trastuzumab). It provide a more comprehensive blockade of HER signaling family and results in greater antitumor activity than either agent alone.
Again, Perjeta is not a cure, added to standard treatment with Herceptin. Perjeta gives the "average" breast cancer patient only about six months more of calm before the disease starts to stir again. Given the limited benefit, the price is startling. A full course of the drug combination will cost about $188,000.
Best of luck!
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