Medical Oncology’s Nibs and Mabs

Targeted therapy is changing cancer treatment. 

Its a great time to be an oncologist. Tremendous toys!  Hats off to modern science-- if we forget about costs & exclusivity for a minute, we’d be dizzily restructuring our ongoing protocols.

Normal tissues grow & die in a controlled manner. They rely upon interactive signals and factors to initiate, then complete, important functions. In fact, the way cells obediently "go jump in the lake" on command may give you nightmares about dictatorships and the natural order of things. Cancer is the disease marked by loss of that order. The signals get messed up and the factors are mis-used. The abnormal cells keep growing & refuse to die. Sounds like a rebellion, doesn’t it?

Targeted therapy is one cool way to "salvage" the rebels.  It is great stuff! When you specify a tumor target, you avoid many side effects resulting from normal tissue injury or death (such as those caused by radiation & most chemotherapy agents).  Its not an entirely new idea.  Hormonal manipulation has been around for some time for tumors which express the corresponding receptors on their cell surfaces.  What’s new is that The Human Genome Project and other humongous brain trusts have clarified new tumor-specific targets for similar manipulation.  We can now zero in on teeny molecules inside of & exterior to the cancer cell, even on its blood supply.  By doing so, we are able to hinder cancer cell function, growth, & propagation while largely avoiding damage to other tissues.

I use a mnemonic to broadly classify the manner by which these targeted agents do their thing and, consistent with my personality, its by no means 100% scientific.  Nibs (imatinib, gefitinib, erlotinib, lapatinib, sunitinib, sorafenib, etcetera) interfere with signalling pathways which control functions like cell proliferation & death.  Mabs are antibodies that attach to predetermined molecules. They can block receptors to prevent growth factors from acting on the target cell, incite direct cell lysis by the patient’s own immune response, act as guides for killer isotopes attached to them, and so on. (Trastuzumab, bevacizumab, cetuximab, ibritumomab, alemtuzumab, rituximab). Then there are the cancer vaccines, which may someday effectively build up & use patients’ defenses against their own malignancies.

Can these amazing drugs take the place of chemotherapy? In a few instances, yes- esp in those malignancies where chemo doesn’t work well anyway, like Gleevec for GIST & Sutent for renal cell cancer. In many cases, however, the 2 treatment types are complementary or even synergistic, i.e., the benefit when given together is more than the sum of one treatment’s effect. Are they curative in very advanced disease? No. They do improve on the success rates of conventional therapies in more limited stages (as in "adjuvant" herceptin in breast cancer or rituximab added to chemo in certain lymphomas).

Thank you ImClone, Amgen, Genentech et al for the gazillions you invested in R&D. We wish you the Big Payoff that you deserve, so that you can do even more research. Through such efforts, cancer control & therapy may someday be a matter of prescribing the right pill.

But… when will the Indians & Chinese do decent clones for the benefit of those who don’t receive state health subsidies?  Politics again. Ahh me.

Image from Harper’s Weekly; 5 March, 1864


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