Operational strategies in US cancer centers of excellence that support the successful accrual of racial and ethnic minorities in clinical trials.

BACKGROUND: Study populations in clinical research must reflect US changing demographics, especially with the rise of precision medicine. However, racial and ethnic minority groups (REMGs) have low rates of participation in cancer clinical trials. METHODS: Criteria were developed to identify cancer centers able to accrue a higher than average proportion of REMGs into clinical trials. Comprehensive interviews were conducted with leaders of these cancer centers to identify operational strategies contributing to enhanced accrual of REMGs. RESULTS: Eight US cancer centers reported a REMG accrual rate range in cancer research between 10 and 50% in a 12-month reporting period and met other criteria for inclusion. Fourteen leaders participated in this assessment. Key findings were that centers: had a metric collection and reporting approach; routinely captured race and ethnicity data within databases accessible to research staff; had operational standards to support access and inclusion; developed practices to facilitate sustained patient participation during clinical trials; had strategies to decrease recruitment time and optimize clinical study design; and identified low-resource strategies for REMG accrual. There was also a clear commitment to establish processes that support the patient's provider as the key influencer of patient recruitment into clinical trials. CONCLUSION: We have identified operational practices that facilitate increased inclusion of REMGs in cancer trials. In order to establish a sustainable cancer center inclusion research strategy, it is valuable to include an operational framework that is informed by leading US cancer centers of excellence.

Identification of five novel modifier loci of Apc(Min) harbored in the BXH14 recombinant inbred strain.

Every year thousands of people in the USA are diagnosed with small intestine and colorectal cancers (CRC). Although environmental factors affect disease etiology, uncovering underlying genetic factors is imperative for risk assessment and developing preventative therapies. Familial adenomatous polyposis is a heritable genetic disorder in which individuals carry germ-line mutations in the adenomatous polyposis coli (APC) gene that predisposes them to CRC. The Apc ( Min ) mouse model carries a point mutation in the Apc gene and develops polyps along the intestinal tract. Inbred strain background influences polyp phenotypes in Apc ( Min ) mice. Several Modifier of Min (Mom) loci that alter tumor phenotypes associated with the Apc ( Min ) mutation have been identified to date. We screened BXH recombinant inbred (RI) strains by crossing BXH RI females with C57BL/6J (B6) Apc ( Min ) males and quantitating tumor phenotypes in backcross progeny. We found that the BXH14 RI strain harbors five modifier loci that decrease polyp multiplicity. Furthermore, we show that resistance is determined by varying combinations of these modifier loci. Gene interaction network analysis shows that there are multiple networks with proven gene-gene interactions, which contain genes from all five modifier loci. We discuss the implications of this result for studies that define susceptibility loci, namely that multiple networks may be acting concurrently to alter tumor phenotypes. Thus, the significance of this work resides not only with the modifier loci we identified but also with the combinations of loci needed to get maximal protection against polyposis and the impact of this finding on human disease studies.