Improvements in cancer screening, early detection, and treatment are resulting in increased numbers of patients cured of cancer. These persons face a wide range of medical and psychosocial challenges that need to be planned for and appropriately managed.

The antitumor activities of the novel adenosine monophosphate-activated protein kinase (AMPK) activator, OSU-53, were assessed in in vitro and in vivo models of triple-negative breast cancer. OSU-53 directly stimulated recombinant AMPK kinase activity (EC₅₀, 0.3 μm) and inhibited the viability and clonogenic growth of MDA-MB-231 and MDA-MB-468 cells with equal potency (IC₅₀, 5 and 2 μm, respectively) despite lack of LKB1 expression in MDA-MB-231 cells. Nonmalignant MCF-10A cells, however, were unaffected. Beyond AMPK-mediated effects on mammalian target of rapamycin signaling and lipogenesis, OSU-53 also targeted multiple AMPK downstream pathways. Among these, the protein phosphatase 2A-dependent dephosphorylation of Akt is noteworthy because it circumvents the feedback activation of Akt that results from mammalian target of rapamycin inhibition. OSU-53 also modulated energy homeostasis by suppressing fatty acid biosynthesis and shifting the metabolism to oxidation by up-regulating the expression of key regulators of mitochondrial biogenesis, such as a peroxisome proliferator-activated receptor γ coactivator 1α and the transcription factor nuclear respiratory factor 1. Moreover, OSU-53 suppressed LPS-induced IL-6 production, thereby blocking subsequent Stat3 activation, and inhibited hypoxia-induced epithelial-mesenchymal transition in association with the silencing of hypoxia-inducible factor 1a and the E-cadherin repressor Snail. In MDA-MB-231 tumor-bearing mice, daily oral administration of OSU-53 (50 and 100 mg/kg) suppressed tumor growth by 47–49% and modulated relevant intratumoral biomarkers of drug activity. However, OSU-53 also induced protective autophagy that attenuated its antiproliferative potency. Accordingly, cotreatment with the autophagy inhibitor chloroquine increased the in vivo tumor-suppressive activity of OSU-53. OSU-53 is a potent, orally bioavailable AMPK activator that acts through a broad spectrum of antitumor activities.

CONTEXT AND QUESTION(S) ASKED: The number of cancer survivors is increasing exponentially. Currently there about 15 million cancer survivors, and by 2025, there will be nearly 20 million. Who will provide survivorship care, what are evidenced-based or best care practices, what are best methods to disseminate this information and assess its impact on physician practice, and what are the most cost-effective health care delivery models to serve the majority of survivors? SUMMARY ANSWER: The ASCO Survivorship Committee in collaboration with the ASCO Professional Development Committee developed a core curriculum and core competencies for physicians, allied health professionals, training programs, and policymaking organizations. Adapted from Institute of Medicine recommendations for survivorship care, the core curriculum and competencies include the following subheadings: surveillance for recurrence and second malignancies, long-term and late effects, health promotion and prevention, psychosocial well-being, special populations including adolescent and young adult survivors, older adult cancer survivors, caregivers of cancer survivors and communication and care coordination. METHODS: An environmental scan (a process that systematically surveys and interprets relevant data to identify opportunities and barriers) for survivorship was performed. Although survivorship content exists in various courses, conferences, guidelines, and Web-based applications, the information is incomplete and not easily found. Hence, there was a need for this content to be easy to access and available in one place. Content experts formulated the individual sections based on the environmental scan and their knowledge of the various subheadings. BIAS, CONFOUNDING FACTOR(S), DRAWBACKS: Both an environmental scan and a comprehensive literature review have standard methodologies. The differences are in scope; an environmental scan is more like an overview, and the standard literature review is more granular. For this article, we felt that environmental scan better served the purpose of developing a survivorship core curriculum and competencies. REAL-LIFE IMPLICATIONS: Survivorship care is one the most challenging problems oncologists face today and in the near future. Fundamental to the relatively new field of survivorship care is this core curriculum and competencies, which provide the framework necessary to generate appropriate referrals depending on local practices and expertise.

Purpose: Skeletal-related events (SREs) such as pathologic fracture, spinal cord compression, or the necessity for radiation or surgery to bone metastasis cause considerable morbidity, decrements in quality of life, and costs to the health care system. The results of a recent large randomized trial (Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology [CALGB/Alliance 70604]) showed that zoledronic acid (ZA) every 3 months was noninferior to monthly ZA in reducing the risks of SREs. We sought to determine the cost-effectiveness (CE) of monthly ZA, ZA every 3 months, and monthly denosumab in women with breast cancer and skeletal metastases. Methods: Using a Markov model, costs per SRE avoided were calculated for the three treatments. Sensitivity analyses were performed where denosumab SRE probabilities were assumed to be 50%, 75%, and 90% lower than the ZA SRE probabilities. Quality-adjusted life-years were also calculated. The analysis was from the US payer perspective. Results: The mean costs of the denosumab treatment strategy are nine-fold higher than generic ZA every 3 months. Quality-adjusted life-years were virtually identical in all the three treatment arms; hence, the optimal treatment would be ZA every 3 months because it was the least costly treatment. The sensitivity analyses showed that relative to ZA every 3 months, the incremental costs per mean SRE avoided for denosumab ranged from $162,918 to $347,655. Conclusion: ZA every 3 months was more CE in reducing the risks of SRE than monthly denosumab. This analysis was one of the first to incorporate the costs of generic ZA and one of the first independent CE analyses not sponsored by either Novartis or Amgen, the makers of ZA and denosumab, respectively. ZA every 3 months is the more CE option and more reasonable alternative to monthly denosumab.