Journal Watch

New strategy for reducing tumor growth

Ann Richmond, PhD, and colleagues have discovered that blocking a certain signaling pathway boosts antitumor immunity and reduces tumor growth and metastasis in models of breast cancer and melanoma. The findings, reported Dec. 18, 2020, in the journal Cancer Immunology Research, add mechanistic insight and support for the therapeutic potential of drugs that are currently being tested in clinical trials for various types of cancer. The researchers, led by Jinming Yang, PhD, staff scientist, and Chi Yan, PhD, research instructor in Pharmacology, showed in a mouse model that targeting CXCR2 in myeloid cells ablated the trafficking of myeloid-derived suppressor cells, which suppress T cell-mediated immune response. The study results demonstrated enhanced immune response to a developing tumor.

Study suggests reconsideration of breast cancer treatment protocol

For women over age 70 with early-stage breast cancer, current guidelines from the U.S. National Comprehensive Cancer Network recommend omitting radiotherapy after breast-conserving surgery. However, Xiao-Ou Shu, MD, PhD, MPH, Fei Wang, MD, PhD, and colleagues analyzed survival data, which indicated patients who received no radiotherapy had a higher mortality rate than those who received the treatment. They reported Sept. 15, 2020, in the International Journal of Cancer that the five-year survival rate was 83.8% for those who received radiotherapy versus 71.2% for those who did not.

Screening younger women for hereditary cancers may be cost effective

Population-wide screening for genetic variants linked to hereditary breast and ovarian cancer may be cost effective in women between the ages of 20 and 35, according to a study published Oct. 29, 2020, in JAMA Network Open. However, screening for older women was not cost-effective, the researchers found, since the majority of risk-reducing mastectomies and salpingo- oophorectomies occur before age 50 and the majority of hereditary breast and ovarian cancers occur after 50. Older women who learn they are at risk have a smaller window of time to take action. Josh Peterson, MD, MPH, is a principal investigator for RISE (Rational Integration of clinical Sequencing) consortium, which launched the study.

Polygenic risk scores determined for more types of cancer

Wei Zheng, MD, PhD, and colleagues have applied polygenic risk scores (PRS), which summarize the combined effect of multiple genomic variants, to predict risk for common cancers including those of the prostate, breast and colon. Now they have applied the technique to evaluate nine fewer common cancers, including melanoma, glioma and chronic lymphoid leukemia, which account for approximately 24% of cancer deaths globally. Using genome-wide association studies data gathered from 400,807 participants of European descent in the UK Biobank, the researchers determined through PRS that 63% of participants had a greater than twofold elevated risk for at least one of the cancers. The findings were published July 9, 2020, in the International Journal of Cancer.

Gene network for leukemia factor

Transcription factors — proteins that regulate gene expression — play critical roles in cell fate decisions and are frequent targets of mutation in a variety of human cancers. The transcription factor AML1-ETO is generated by the most frequent chromosomal translocation in acute myeloid leukemia.

Understanding how AML1-ETO and other transcription factors contribute to human disease requires the identification of their direct gene targets, but traditional methods are time-consuming and make it difficult to distinguish direct from secondary changes.

Kristy Stengel, PhD, Scott Hiebert, PhD, and colleagues have now devised a chemical genetic approach that speeds transcription factor analysis from days to minutes.

Reporting in Molecular Cell, the researchers applied the new approach to analysis of AML1-ETO. They defined a small core network of about 60 direct AML1-ETO-regulated genes. The network included critical mediators of myeloid differentiation and cell fate decisions. The research team demonstrated that AML1-ETO represses this small network and impairs myeloid differentiation. The findings also provided mechanistic insights that point to new targets and therapeutic strategies for acute myeloid leukemia.