A series of compounds were designed and synthesized as antagonists of cIAP1/2, ML-IAP, and XIAP based on the N-terminus, AVPI, of mature Smac. Compound 1 (GDC-0152) has the best profile of these compounds; it binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2 with Ki values of 28, 14, 17 and 43 nM, respectively. These compounds promote degradation of cIAP1, induce activation of caspase-3/7, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. Compound 1 inhibits tumor growth when dosed orally in the MDA-MB-231 breast cancer xenograft model. Compound 1 was advanced to human clinical trials and it exhibited linear pharmacokinetics over the dose range (0.049 to 1.48 mg/kg) tested. Mean plasma clearance in humans was 9 ± 3 mL/min/kg and volume of distribution was 0.6 ± 0.2 L/kg.

This study examined the long-term impact of parental cancer during childhood. Nineteen female and 8 male adults who had a parent with terminal or nonterminal cancer during childhood participated in face-to-face interviews during which they discussed how their parent's cancer affected their lives. Their interview responses were transcribed and analyzed using a constant comparative method of analysis. Posttraumatic growth experiences were reported by 44% of participants, and 59% reported adverse consequences. Future research should examine ways to identify factors that can help affected children experience posttraumatic growth while minimizing the adverse consequences of having a parent with cancer.

This study examined perceived social support among children of parents diagnosed with cancer. Twenty-nine participants, ages 18-38, who had been children when one of their parents was diagnosed with cancer provided demographic information and participated in an interview about the impact of their parent's illness on their lives. Five common themes characterized participants' perceived social support received during their parent's illness: (a) listening and understanding; (b) encouragement and reassurance; (c) tangible assistance; (d) communication about cancer and treatment; and (e) engaging in normal life experiences. Depending on the circumstances, however, a given type of social support was perceived to be helpful to some, while perceived by others as ineffective or detrimental. Differences in respondents' perceptions of the effects of specific forms of received social support speak to the need for individualized support for children of cancer patients based upon each child's specific needs and circumstances.

No abstract

This study examined predictors of posttraumatic stress disorder (PTSD) symptoms in adults who, as children, had a parent diagnosed with cancer. Possible predictors of adulthood PTSD examined were peritraumatic dissociation, satisfaction with social support, coping through denial, behavioral disengagement and self-distraction, and whether or not the parent died. Thirty research participants (20 women and 10 men, ages 18-38) were recruited who were 8-17-years old at the time of a parent's cancer diagnosis. Each participant completed measures of their current PTSD symptoms in response to their parent's cancer, peritraumatic dissociative experiences, demographic characteristics, and satisfaction with social support and use of coping strategies at the time of their parent's cancer diagnosis. Seventeen percent met screening criteria for likely PTSD. As hypothesized, PTSD symptoms were strongly and positively correlated with peritraumatic dissociation. Furthermore, PTSD symptoms were greater among females and were related to greater use of denial and behavioral disengagement and to less satisfaction with social support. These results suggest that health care providers need to recognize symptoms of peritraumatic dissociation in the children of parents who are diagnosed with cancer so that steps can be taken to minimize the children's development of PTSD that may extend into their adult lives.