ATYPICAL RESPONDERS LANDSCAPE REVIEW ∙ OCTOBER, 2017 25 Cancer Against All Odds” by Kelly A. Turner and the mainstream media Discover Magazine’s “The Body Can Beat Terminal Cancer — Sometimes” (read more). An important caveat is that due to a dearth of scientific studies, researchers and clinicians do not know how or if the therapy is related to the outcome, or if the same response would be reproducible in other patients. In addition, stories of patients who tried such therapies but did not survive are not readily available, and a recent study from the Yale School of Medicine determined that cancer patients who use only alternative therapies are twice as likely to die as those who undergo conventional treatment [69] (read more). Whether the alternative product and/or practice itself, the patient’s unique physiology, the placebo effect, or a combination of these factors working together contribute to an unexpectedly favorable (or unfavorable) outcome remains unknown. Further evidence-based studies are warranted. Some therapies such as the use of certain diets, supplements, and protocols can be adopted in either an integrative or alternative setting. Testing in one setting may validate the use of a given therapy in another setting. One example is Iscador® , which has been used as a CIM therapy as described above, as well as in alternative settings (read more). The study of alternative therapies requires careful consideration of whether the patient has exhausted the list of viable available standard therapies, the patient’s willingness to try an unproven therapy, ease of access to the new treatment, funding sources, verification that the new therapy is relatively or completely non-toxic, and valid methodology for measuring and replicating patients’ responses. As with other clinical studies, thoughtful study design must be combined with ethical issues relative to the life expectancy and QOL of the patient. A priori determination of what could be learned about the relationship between the alternative therapy in question and a potential clinical benefit must be carefully considered in conjunction with the patient’s wishes. Prognostic and Diagnostic Assay Use in Atypical Response Research One of the confounding aspects of cancer research is that seemingly similar tumors respond differentlytoagiventherapy. Sometumorsaremoresensitivetocertaindrugsthanothers,andrecent studies are beginning to elucidate the mechanisms of chemosensitivity and chemoresistance. For example, breast cancer tumors that express high levels of pyruvate M2 kinase are more sensitive to Ellence® (epirubicin) and Efudex® , Carac® , and Fluoroplex® (5-fluorouracil) than tumors that express low levels of the kinase [70]. A protein called RECK can be downregulated in breast cancer cells, and restoration of higher levels of RECK may increase the chemosensitivity of breast cancer cells [71]. The microRNA MiR-139-5p regulates drug resistance and the viability of breast cancer cells by regulating expression of its target, Notch 1 [72]. A newly identified gene called MACROD2 confers resistance to Nolvadex® (tamoxifen) in breast cancer cells and estrogen-independent growth when overexpressed. Expression of MACROD2 can change as breast cancer progresses [73].