Recent Publications

Exploring the Potential of Drug Response Assays for Precision Medicine in Ovarian Cancer

One of the major challenges in the treatment of cancer are differential responses of patients to existing standard of care anti-cancer drugs. These differential responses may, in part, be due to a diverse range of genomic, epigenomic, proteomic, and metabolic alterations among individuals suffering from the same type of cancer. Precision medicine is an emerging approach in cancer therapeutics...

Matched sequential tumor molecular profiling in solid malignancies may impact clinical practice

To determine if performing repeat tumor molecular profiling in solid malignancies over time can identify new findings that impact clinical care...

Expression of stromal progesterone receptor and differential methylation patterns in the endometrium may correlate with response to progesterone therapy in endometrial complex atypical hyperplasia

Progesterone therapy is a viable treatment for complex atypical hyperplasia (CAH) and endometrial adenocarcinoma, though reliable molecular determinants of response are not available. To explore if analysis of pre-therapy endometrial biopsies could yield biomarkers of response to progesterone...

A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids

Tumor organoids maintain cell–cell interactions, heterogeneity, microenvironment, and drug response of the sample they originate from. Thus, there is increasing interest in developing tumor organoid models for drug development and personalized medicine applications. Although organoids are...

A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas.

Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated amyloid-like state. Here we show that...

Tubal Ligation Induces Quiescence in the Epithelia of the Fallopian Tube Fimbria.

Tubal ligation keeps the fimbriated end of the fallopian tube intact while interrupting the conduit for sperm and egg between the uterus and ovary. Tubal ligation is associated with an approximately 20% decreased risk of high-grade serous ovarian cancers, which mounting evidence suggests arise from the distal fallopian tube epithelium. We postulated that...

Low levels of circulating estrogen sensitize PTEN-null endometrial tumors to PARP inhibition in vivo.

Earlier in vitro work demonstrated that PARP inhibition induces cell death in PTEN-null endometrial cancer cell lines, but the in vivo therapeutic efficacy of these agents against endometrial cancer remains unknown. Here, we test the efficacy of...

Progesterone receptor signaling in the microenvironment of endometrial cancer influences its response to hormonal therapy.

Progesterone, an agonist for the progesterone receptor (PR), can be an efficacious and well-tolerated treatment in endometrial cancer. The clinical use of progesterone is limited because of the lack of biomarkers that predict hormone sensitivity. Despite its efficacy in cancer therapy, mechanisms and site of action for progesterone remain unknown. Using an in vivo endometrial cancer mouse model driven by clinically relevant genetic changes but dichotomous responses to hormonal therapy, we show...

Cell-autonomous activation of the PI3-kinase pathway initiates endometrial cancer from adult uterine epithelium.

Epithelial-specific activation of the PI3-kinase pathway is the most common genetic alteration in type I endometrial cancer. In the majority of these tumors, PTEN expression is lost in the epithelium but maintained in tumor stroma. Currently reported PTEN knockout mouse models initiate type I endometrial cancer concomitant with loss of PTEN in both uterine epithelium and stroma. Consequently, the biologic outcome of selectively activating the PI3-kinase pathway in the endometrial epithelium remains unknown. To address this question, we...

Stem-like epithelial cells are concentrated in the distal end of the fallopian tube: a site for injury and serous cancer initiation.

The reproductive role of the fallopian tube is to transport the sperm and egg. The tube is positioned to act as a bridge between the ovary where the egg is released and the uterus where implantation occurs. Throughout reproductive years, the fallopian tube epithelium undergoes repetitive damage and regeneration. Although a reservoir of adult epithelial stem cells must exist to replenish damaged cells, they remain unidentified. Here, we report...

Estrogen and progesterone together expand murine endometrial epithelial progenitor cells.

Synchronous with massive shifts in reproductive hormones, the uterus and its lining the endometrium expand to accommodate a growing fetus during pregnancy. In the absence of an embryo the endometrium, composed of epithelium and stroma, undergoes numerous hormonally regulated cycles of breakdown and regeneration. The hormonally mediated regenerative capacity of the endometrium suggests that signals that govern the growth of endometrial progenitors must be regulated by estrogen and progesterone. Here, we report...

SUPPORT RESEARCH

Donate

Every donation is gratefully accepted and will be put to use on the work of the lab. There are many ways to donate, and all make a difference. If you share our passion for finding better treatments for women’s cancer, please consider giving hope by donating to this important cause.

©2017 G.O. Discovery Lab