NEW FINDINGS — GENETICS AND GENOMICS IN THE CLINIC
Finding the Y in bladder cancer Cancer cells accumulate genetic changes ranging from an individual DNA letter to missing or extra chromosomes. A common genetic change in the cancer cells of men, particularly in bladder cancer, is a missing Y chromosome. The loss of the Y chromosome (LOY) is associated with a worse prognosis than cancers with the Y chromosome intact. A recent study used a mouse
Topical gene therapy offers new hope for genetic skin conditions Dystrophic epidermolysis bullosa (DEB) is a rare disease that causes affected individuals to develop severe skin blisters after minor trauma, such as walking around and performing everyday tasks. It is caused by genetic changes in the COL7A1 gene, which
encodes type VII collagen. Collagens are responsible for helping hold the layers of skin together. Their dysfunction in DEB impacts the integrity of the skin, leading to blisters. A new treatment for DEB was recently approved for clinical use.
bladder cancer model system to compare the growth of tumor cells with and without a Y chromosome present. The LOY cancer cells grew two times faster than the cancer cells with a Y chromosome. However, when the same study was conducted in mice with a compromised immune system, the cancer cells grew at the same rate regardless of Y chromo- some status. This indicates that the host immune system affects the difference in tumor growth rate. The tumors with Y chromosomes elicited
The treatment is a virus-based gene therapy that delivers instruc- tions for making functional type VII collagen in a gel applied di- rectly to the skin. The phase 3 trial enrolled 31 patients with DEB. For each patient, one blistering wound was randomly chosen for gene therapy, while another received a placebo. After six months of treatment and data collection, 67% of wounds treated with gene therapy experienced complete healing compared to 22% of wounds in the placebo group. The treatment was even successful on wounds that had been present for more than ten years. The effects of the treatment are isolated to the skin cells present at the time of treatment application, meaning the treatment must continue to be applied over time as new blisters form. However, this newly approved treatment provides hope for wound relief for patients affected by DEB. n
a greater T-cell immune response, while LOY tumors can escape anti-tumor immunity by putting host T-cells in a dysfunctional, exhausted state. These findings also indicate that LOY tumors may be good candidates for treatment with immunotherapy. Certain types of immunotherapy work by helping keep T cells “turned on” and not exhausted. Knowing whether male cancer cells contain their Y chromosome could help doctors and patients better understand the cancer’s prognosis and best treatment strategy. n REFERENCE: Abdel-Hafiz, H.A., Schafer, J.M., Chen, X. et al. Y chromosome loss in cancer drives growth by evasion of adaptive immunity. Nature (2023) 619: 624–631 (2023). doi.org/10.1038/s41586-023-06234-x
REFERENCE: Dhillon S. Beremagene Geperpavec: First Approval. Drugs (2023) 83(12):1131-1135. doi: 10.1007/s40265-023-01921-5
Targeting aging with anti-cancer tech
treatment in vivo in both mouse and non-hu- man primate models. Results showed that the treatment successfully eliminated senescent cells and that the aged mice had improvements in liver, kidney, heart, and metabolism
As we age, our bodies go through many physical and physiological changes. One of these changes is the accumulation of senescent cells. These cells stop dividing but do not undergo cell death as they should. Instead, the cells persist and continue to release chemicals that can wreak havoc on the body. The build-up of senescent cells is believed to contribute to many age-related diseases. Finding ways to target and remove senescent cells is an active area of research that could prevent, delay, or even reverse disease symptoms. A recent study tested the use of genetically engineered cells called CAR T-cells, designed to target a specific protein, NKG2DL, which is highly expressed in senescent cells and not in normal cells. Researchers tested CAR T
biochemical markers. While more research is needed before the treatment can be used for age-related diseases in humans, NKG2DL CAR T-cells have already been studied in the field of cancer and found to be safe with few side effects. n REFERENCE: Dong Yang et al. NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates. Sci. Transl. Med (2023), 15, eadd1951. doi:10.1126/sci- translmed.add1951
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