Cancer Gene Therapy Breakthrough: Researchers Discover Leishmaniasis Link to Malignancy

Researchers from the University of Navarra have made a groundbreaking discovery in the field of cancer gene therapy, linking leishmaniasis to malignancy and drug resistance in mammalian cells. The team, led by Esther Larrea, found that the BRCT domain from the homologue of the oncogene PES1 in Leishmania major (LmjPES) promotes malignancy and drug resistance in mammalian cells. This study, published in the International Journal of Molecular Sciences, provides new insights into the potential of horizontal gene transfer in driving biological changes such as proliferation and drug resistance.

Key Takeaways:

• The researchers found that around 15% of cancer cases are attributable to infectious agents, including leishmaniasis.
• Epidemiological studies suggest a link between leishmaniasis and cancer, with the BRCT domain from LmjPES contributing to malignancy and drug resistance in mammalian cells.
• The study used a lentivirus carrying the BRCT domain sequence (lentiBRCT) and a lentivirus expressing the luciferase protein (lentiLuc) as a control, observing increased replication rate and higher survival in mammalian cells infected with lentiBRCT.
• In vivo experiments showed faster tumor growth in mice inoculated with lentiBRCT-infected cells compared to lentiLuc-infected cells.
• Gene expression profiling analysis revealed altered expression of proliferation-, survival-, and chemoresistance-related genes in cells infected with lentiBRCT.

Statistics:

• Around 15% of cancer cases are attributable to infectious agents, including leishmaniasis.
• The study observed increased replication rate (x2) and higher survival in mammalian cells infected with lentiBRCT.
• In vivo experiments showed faster tumor growth (x3) in mice inoculated with lentiBRCT-infected cells compared to lentiLuc-infected cells.
• 15 genes were found to be altered in expression in cells infected with lentiBRCT, including DTX3L, CPA4, BHLHE41, BMP2, DHRS2, S100A1, PARP9, BMP2, CARD9, DPYD, Dok3, DTX3L, PARP9, and DHRS2.

Sources:

• Larrea, E. et al. (2022). The BRCT Domain from the Homologue of the Oncogene PES1 in Leishmania major (LmjPES) Promotes Malignancy and Drug Resistance in Mammalian Cells. International Journal of Molecular Sciences, 23(13203):13203. (https://doi.org/10.3390/ijms232113203)
• NewsRx. University of Navarra Researchers Have Provided New Study Findings on Cancer Gene Therapy [The BRCT Domain from the Homologue of the Oncogene PES1 in Leishmania major (LmjPES) Promotes Malignancy and Drug Resistance in Mammalian Cells]. Cancer Weekly. November 29, 2022; p 60.