Nature Immunology: A new mechanism of breast cancer drug resistance

Scientists from Università Cattolica in Rome and colleagues from the IIGM Foundation (part of the Candiolo Institute in Turin) have discovered in breast cancer a new mechanism of drug resistance that leads to the formation
of cancer stem cells (cells that nourish tumors and lead to recurrence and metastasis).
They also designed an experimental therapy to bypass or prevent the emergence
of drug resistance.

The findings were published in the journal Natural Immunology
.
The study was coordinated by Antonella Sistigu and Martina Musela of the Department of Translational Medicine and Surgery under the guidance of Professor Ruggero De Maria and Ilio Vitale of the IIGM Foundation of the Italian Institute for Genomic Medicine (affiliated with the São Paulo Foundation), which is located at the Candiolo Institute
of FPO-IRCCS in Candiolo (Turin).
The project is funded by the AIRC Foundation and the Italian Ministry of Health
.

Italian scientists have discovered how tumors evolve and become resistant to treatment during treatment
.
"More specifically," explains Sistigu and Musella, "we have shown that some tumor cells release a set of factors called 'alarm hormones' in the tumor microenvironment at the same time that chemotherapy causes death, which under normal circumstances can alert and activate the immune system
.
" "Paradoxically, however, some of these alarm bells, such as type I interferons, can reprogram residual cancer cells and turn them into cancer stem cells, the deadly reservoir
of tumors.
" For example, these stem cells are responsible for the recurrence and metastasis
of the disease.

Cancer stem cells are out of the control of the immune system and have a high potential
for invasion and attack.

Italian scientists have found that this mechanism of resistance relies on the activation
of a protein called "KDM1B".
KDM1B controls and regulates gene expression
.

After being found in animal models, Ilio Vitale explains: "We studied 5 different groups of patients and confirmed that this mechanism also works
in patients.
"

Finally, in laboratory experiments, scientists found that inhibiting KDM1B can stop the formation of cancer stem cells and improve the effectiveness of treatment.

"Based on these results, we propose a combination therapy (some specific chemotherapy and immunotherapy, as well as experimental drugs that inhibit KDM1B) to prevent the formation and potentially effective targeting of this subset
of stem cells that are resistant to any treatment.
"

Sistigu concludes that the next step in this study will be to evaluate
combination therapies in clinical trials.

Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B