Neural Crest-Like Stem Cell Transcriptome Analysis Identifies LPAR1 in Melanoma Progression and Therapy Resistance.

Metastatic melanoma is challenging to clinically address. Although standard-of-care targeted therapy has high response rates in patients with BRAF-mutant melanoma, therapy relapse occurs in most cases. Intrinsically resistant melanoma cells drive therapy resistance and display molecular and biologic properties akin to neural crest-like stem cells (NCLSC) including high invasiveness, plasticity, and self-renewal capacity. The shared transcriptional programs and vulnerabilities between NCLSCs and cancer cells remains poorly understood. Here, we identify a developmental LPAR1-axis critical for NCLSC viability and melanoma cell survival. LPAR1 activity increased during progression and following acquisition of therapeutic resistance. Notably, genetic inhibition of LPAR1 potentiated BRAFi ± MEKi efficacy and ablated melanoma migration and invasion. Our data define LPAR1 as a new therapeutic target in melanoma and highlights the promise of dissecting stem cell-like pathways hijacked by tumor cells. SIGNIFICANCE: This study identifies an LPAR1-axis critical for melanoma invasion and intrinsic/acquired therapy resistance.

Understanding the biology of sex and gender differences: using subgroup analysis and statistical design to detect sex differences in clinical trials.

In May 2000, a General Accounting Office (GAO) report revealed that although women are now participating in clinical trials in numbers proportionate to their numbers in the general population, data collected in these trials are not routinely analyzed by sex.[1] Without such sex analysis, clinically relevant information about potentially lifesaving treatments could be lost. In July 2001, the Society for Women's Health Research convened a workshop to address strategies for conducting subgroup analyses to detect sex differences. Workshop participants concluded that understanding sex differences will enable medical researchers to design healthcare interventions for both men and women more effectively and that one can plan for and conduct sex analysis without compromising the quality of the study or making the study prohibitively expensive.

Positioning women's health curricula in US medical schools.

PURPOSE: This survey was undertaken to evaluate the status of women's health curricula at US medical schools. METHODS: The Society for Women's Health Research surveyed 125 US medical schools to gather information on the existence of and institutional funding and support for women's health curricula. RESULTS: After a minimum of 2 reminder emails, 68 schools returned completed surveys for a positive response rate of 54.4%. Thirty (44%) schools responded that they currently offered a women's health curriculum; 12 (18%) schools stated that they had plans to develop one. Of the 42 schools that either offered a women's health curriculum or were planning one, two thirds (n = 28) reported having a designated office responsible for overseeing the curriculum; the Associate Dean of Medicine/Associate Dean of the Medical School was most frequently the person responsible for this office. Overall, more than half of the responding schools reported receiving funding for this office either through general medical school funds (15/28) or from a Dean's fund (9/28). CONCLUSIONS: Our findings suggest that while US medical schools have made great strides in training medical students in women's health, schools can do more to ensure that women's health has an "academic home" within their institutions. Further, efforts to secure adequate funding and train a cross-section of faculty in women's health should be increased.