Person:

Longacre, McKenna

Cancers have the ability to develop resistance to traditional therapies, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. This paper outlines the current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and the epithelial-mesenchymal transition, as well as how inherent tumor cell heterogeneity plays a role in drug resistance. It also describes the epigenetic modifications that can induce drug resistance and considers how such epigenetic factors may contribute to the development of cancer progenitor cells, which are not killed by conventional cancer therapies. Lastly, this review concludes with a discussion on the best treatment options for existing drug resistant cancers, ways to prevent the formation of drug resistant cancers and cancer progenitor cells, and future directions of study.

EMT and MET comprise the processes by which cells transit between epithelial and mesenchymal states, and they play integral roles in both normal development and cancer metastasis. This article reviews these processes and the molecular pathways that contribute to them. First, we compare embryogenesis and development with cancer metastasis. We then discuss the signaling pathways and the differential expression and down-regulation of receptors in both tumor cells and stromal cells, which play a role in EMT and metastasis. We further delve into the clinical implications of EMT and MET in several types of tumors, and lastly, we discuss the role of epigenetic events that regulate EMT/MET processes. We hypothesize that reversible epigenetic events regulate both EMT and MET, and thus, also regulate the development of different types of metastatic cancers.

Breast cancer persists as the most common cause of cancer death in women worldwide. Ovarian cancer is also a significant source of morbidity and mortality, as the fifth leading cause of cancer death among women. This reflects the continued need for further understanding and innovation in cancer treatment. Though breast and ovarian cancer usually present as distinct clinical entities, the recent explosion of large-scale -omics research has uncovered many overlaps, particularly with respect to genetic and epigenetic alterations. We compared genetic, microenvironmental, stromal, and epigenetic changes common between breast and ovarian cancer cells, as well as the clinical relevance of these changes. Some of the most striking commonalities include genetic alterations of BRCA1 and 2, TP53, RB1, NF1, FAT3, MYC, PTEN, and PIK3CA; down regulation of miRNAs 9, 100, 125a, 125b, and 214; and epigenetic alterations such as H3K27me3, H3K9me2, H3K9me3, H4K20me3, and H3K4me. These parallels suggest shared features of pathogenesis. Furthermore, preliminary evidence suggests a shared epigenetic mechanism of oncogenesis. These similarities, warrant further investigation in order to ultimately inform development of more effective chemotherapeutics, as well as strategies to circumvent drug resistance.

BACKGROUND: The World Bank has characterized poverty among Panama’s largest indigenous population, the Ngöbe–Buglé, as “abysmal.” In addition, family size is significantly above and age of first conception significantly below the average for Panama. We conducted a Needs Assessment of Family Planning to better understand the preferences, barriers to access, and interplay with local culture and socioeconomic status within this population.

METHODS: We conducted a mixed methods study among the indigenous patient population of a local NGO, Floating Doctors. 70 patients were interviewed using a quantitative survey based upon the DHS Individual Questionnaire. Data was analyzed for two primary outcomes: preferences for family planning and unmet need. In addition, 41 key informant interviews were conducted, with data organized around barriers to access, cultural preferences, and issues of human rights.

RESULTS: Fifty three percent (33/62) of subjects met the DHS criteria for unmet need. Lack of money and access were identified as the most significant barriers to obtaining family planning. Key informant interviews suggested that young motherhood and large family size were significantly impacting issues of local health, education and socioeconomic status.

CONCLUSION: This study reveals a profound unmet need for family planning resources. It also highlights the impact of this need on local education, socioeconomics, and public health. Finally, the data suggests that these disparities may be increasing due in part to complex economic shifts. Family planning may mark a clear starting point by which to empower Ngöbe–Buglé families to reclaim health, cultural, and economic stability.