Missing The Target

I read "Missing the Target" with great interest, and I could not agree more with those who call for "moving beyond targeted therapies when tackling cancer" (C&EN, Oct. 26, 2009, page 20). I disagree, however, with their suggestion that "the time is right to devote resources to approaches that might change cancer into a manageable disease." Common wisdom calls on prevention over cure, so it is imperative to identify the underlying broad causes of cancers and other diseases and worry less about tackling symptoms.

In his book "Freedom from Disease" (St. Martin's Press, 2008), Peter Kash contends that controlled insulin levels are key to a balanced and healthy life. Considering our emotional makeup and the highly varied acute and chronic stresses we experience, I'm not sure how this control can be achieved.

Although humans have built-in evolutionary mechanisms to manage acute stress, we are ill-prepared to handle chronic stress. From a psychoneuroimmunological perspective, Edna M. V. Reiche et al. (Lancet Oncol. 2004, 5, 617) have proposed "that the persistent activation of the hypothalamic-pituitary-adrenal (HPA) axis in the chronic stress response and depression probably impairs the immune response and contributes to the development and progression of some types of cancer." They propose that "consecutive stages of the multistep immune reactions are either inhibited or enhanced as a result of previous or parallel stress experiences, depending on the type and intensity of the stressor" and on other factors.

They assert that, in general, stress and depression "are associated with the decreased cytotoxic T-cell and natural-killer-cell activities that affect processes such as immune surveillance of tumors, and with the events that modulate development and accumulation of somatic mutations and genomic instability. A better understanding of bidirectional communication between the neuroendocrine and immune systems could contribute to new clinical and treatment strategies," they say.

Years ago, my colleagues and I described the characterization of corticotropin-releasing factor/hormone (CRF or CRH), the stress hormone. Soon thereafter, we described the first CRF antagonists. I propose that the latest generations of the potent, long-acting peptidic CRF antagonists may be good drug candidates to reinstate homeostasis. This approach would address the causes rather than the symptoms of conditions prone to remissions and stress-related relapses, including some cancers.

Would nurturing cellular (immune) homeostasis be more effective than inducing cancer cell death through chemotherapy, radiation, or starvation? Can this be achieved? There is emerging evidence that the answers may be, "yes."

Jean E. Rivier
La Jolla, Calif.