Towards precision therapy for ovarian cancer
There is a big push in the cancer research field to develop personalized approaches to cancer treatment, tailoring therapeutic choices based on the genomic makeup of each patient’s cancer. A group of researchers set out to understand ovarian cancer better on a genetic and metabolic level to discover markers of treatment response and potential therapeutic targets. Despite considerable progress in cancer treatments over the last 50 years, ovarian cancer remains the deadliest gynecological cancer in the United States due mainly to inadequate early screening and a high incidence of disease recurrence after treatment. To further complicate matters, ovarian cancer originates from three types of ovarian cells that develop into different tumors, each with its own molecular, morphological, and clinical features. Cancer cells can alter their metabolism to support increased energy use due to their continuous growth and rapid proliferation. Metabolic reprogram- ming is a hallmark of cancer that contributes to resistance to chemotherapy, metastatic potential, and suppression of immune cells, but it has not been widely studied in ovarian cancer. Researchers integrated gene expression and metabolic data from tumors and benign tissue to gain a complete picture of a type of epithelial ovarian tumor called high-grade serous ovarian carcinoma. The group found that many patients had tumor gene expression profiles associated with known targetable pathways, meaning new treatments could be developed. In addition, they identified several promising biomarkers of response to treatment and new therapeutic targets. The study highlights some of the challenges in identifying precision medicine approaches for ovarian cancer patients, but it also supports the use of genomic and metabolic information to help select treatment, predict treatment outcomes, and identify potential new therapeutic targets to achieve better results for ovarian cancer patients. n The laboratory of HudsonAlpha faculty researcher Sara Cooper PhD contributed to this work.
Pap smear to detect distant cancer much earlier Breast and gynecological cancers account for over half of all cancers in women. Despite these overwhelming statistics, cervical cancer is the only one of these cancers with a reliable, early screening strategy in place. The screening test, called Pap smear, uses a small brush to gently remove cells from the surface of the cervix so that they can be examined under a microscope for cell changes that indicate cancer or pre-cancer. Two recent studies suggest that samples collected during routine Pap smears could also be used to detect early warning signs of other types of cancer. The research team developed a new scoring system called the women’s cancer risk identification index (WID-index) to predict ovarian and breast cancer risk. The index is based on DNA methylation levels detected in cervical samples. DNA methylation is a type of modification that changes the expression of the DNA, not the sequence of the DNA. Epigenetic changes like methylation have been identified in normal breast tissue adjacent to a breast tumor and could serve as an early indicator of breast cancer. Researchers analyzed more than 3,000 samples collected during routine Pap smear tests to measure epigenetic changes for 850,000 sites in the genome. Focusing on DNA from epithelial cells, the researchers identified a unique epigenetic signature in people with breast and ovarian cancer. The WID-index using epigenetic data for breast can- cer correctly identified 76 percent of women in a high-risk group, compared to current screening, which identified 47.5 percent of women. The ovarian cancer index identi- fied 71 percent of women under 50 as high-risk. There is currently no ovarian cancer screening method used for women under 50. While more validation is necessary, this study presents a promising screening tool that could help non-invasively detect breast and ovarian cancer much earlier and more precisely than current methods. n REFERENCES: Barrett, J.E., et al. The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples. Nat Commun 13 , 449 (2022). DOI: 10.1038/s41467-021-27918-w Barrett, J.E., et al. The DNA methylome of cervical cells can predict the presence of ovarian cancer. Nat Commun 13 , 448 (2022). DOI: 10.1038/s41467-021-26615-y
REFERENCE: Arend RC, et al. Metabolic Alterations and WNT Signaling Impact Immune Response in HGSOC. Clin Cancer Res . (2022)28(7):1433 1445. DOI: 10.1158/1078-0432.CCR-21-2984
Breast cancer and cholesterol Triple-negative breast cancer (TNBC) is a subtype characterized by the lack of three cell surface receptors (estrogen receptor, progesterone receptors, and human epidermal growth factor (HER2) receptor) commonly found in breast can- cer. Patients with TNBC have a higher death rate than patients with other types of breast cancer because there are fewer effective treatments, and it frequently spreads to other organs, a process called metastasis. A group of scientists studying TNBC metastasis discovered a potentially promising treatment. The team was looking for secreted factors responsible for the cells’ ability to migrate to the lungs. They identified a group of small molecules called chemokines that increased in TNBC cells prone to metas- tasis. Further analysis revealed that these chemokines stimulate fibroblast cells in the lungs to secrete different types of cytokines that prompt cancer cells in the lung to produce cholesterol. The cholesterol induces the forma- tion of new blood vessels, which is vital for the growth of metastatic cells. Many drugs are already on the market for lowering cholesterol. Scien- tists administered one such drug, simvastatin, to mice using nanoparticles that targeted the drug to tumor cells. Mice who received the treatment had reduced blood vessel growth and fewer metastatic nodules than control mice. Although the results still need to be validated in humans, it is an exciting study that could provide physicians with another tool in their toolkit to combat TNBC and cancer metastasis. n REFERENCE: Han, B., et al. A chemokine regulatory loop induces cholesterol synthesis in lung-colonizing triple-negative breast cancer cells to fuel metastatic growth. Mol Ther (2021) 30:2, 672-687. DOI: 10.1016/j.ymthe.2021.07.003
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