Genomic landscape of pediatric RMS highlighting candidate alterations. Demographic characteristics, histologic subtypes, and selected genes with copy number alterations or somatic mutations across 147 rhabdomyosarcoma cases. Unique sample identifier and sequencing platform. Sex, males in blue, females in pink. Age, years at diagnosis divided into less than 5 years and greater than 5 years. Histologic diagnosis, red, alveolar; blue, embryonal including spindle and botryoid subtypes; gray, RMS not otherwise specified. Mixed alveolar and embryonal histology in green. Copy number gains and losses for selected genes. Blue, losses; red, gains; green, loss of heterozygozity. Selected genes with somatic mutations. Purple, fusion protein; black, missense; orange, nonsense/splice site/indel mutations [from Shern et al. (2014) with permission].

mSWI/SNF chromatin remodeling complexes in human cancer. Mammalian SWI/SNFcomplexes are separated into two separate forms: BRG1/BRM associated factor (BAF or SWI/SNF-A) and polybromo-associated BAF (PBAF or SWI/SNF-B). BAF and PBAF complexes share numerous subunits, including both ATPases BRG1 and BRM (depicted in red). BAF and PBAF differ from one another by incorporation of key peripheral subunits (depicted in green). Mutations in the genes encoding mSWI/SNF complex subunits are present in over 20% of human cancers, with specific subunits mutated in specific malignancies [from St Pierre and Kadoch (2017) with permission].

Heat map representation of the activity of signaling inhibitors screened by the PPTP against sarcoma xenografts. Drugs are shown in the left column and sarcoma models in the top rows [from Geier et al. (2015) with permission].

Objective response rates (ORR) were calculated for all tumor models tested for a particular drug (n = 1 to n = 55) for different studies, based upon the group median response. Red, responses predicted from a randomly chosen single mouse are plotted against group median response; blue, the single mouse ORR mean ORR correlation based on 1000 single mouse samples [from Murphy et al. (2016) with permission].

Production of CAR-T cells in a GMP facility. Production begins with (1) leukapheresis of the patient and is then followed by selection of T cells (2), and their activation, from the leukapheresis product by positive selection with a CD3 antibody ± anti-CD28 antibody. After a few days the activated T cells are incubated with retroviral supernatant to transfer the CAR gene (3). Expansion, washing, and formulation result in infusion back into the patient [from Davila et al. (2014a) with permission].