Oncotarget published this trending research paper on March 30, 2021, entitled, "Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine" by researchers from the University of Texas MD Anderson Cancer Center, Houston, Texas.
Triple-negative breast cancer (TNBC) accounts for 10-15% of all breast cancers. “Triple-negative” refers to the lack of HER2 protein and estrogen and progesterone receptors. This means that TNBC cannot be treated with hormone inhibition and must be treated with conventional chemotherapy. In addition, many of these highly adaptable breast cancer cells can opportunistically switch between proliferation and quiescence. This highly-heterogeneous cancer is very difficult to treat, and TNBC patients frequently develop drug resistance and relapse after neoadjuvant therapies.
The researchers from the University of Texas MD Anderson Cancer Center conducted a research study in hopes of developing a safe and effective therapeutic combination to treat resistant triple-negative breast cancer.
“Evidence suggests that SUM149-metabolic adaptable (MA) cells are a suitable model of resistant human triple-negative breast cancer (TNBC) cells that can survive bottlenecks in the body, including therapeutic interventions, by opportunistically switching between quiescence and cell proliferation.”
In this in vitro study, researchers cultured three highly drug-resistant and metastatic progenitor-like TNBC cell lines with a difficult phenotype—opportunistic switching between quiescence and proliferation. Researchers focused on designing a safe treatment that is effective in both low- and high-risk patients. The researchers note that it was critical to their study that the regimen is proven safe to administer to patients for early use in the minimal residual disease (MRD) stage after surgery, and before clinical metastasis is detected.
“For a potential therapy to be suitable at the MRD stage, it must be safe (an important criterion prior to clinical relapse) and disrupt heterogeneous progenitor-like cancer cells that evolve into clinical metastases.”
Two chemotherapy and immunosuppressive drugs (ribonucleoside analogues) were tested on the cell lines at low doses for the sake of viability in the MRD stage: 6-mercaptopurine (6-MP) and 5-azacitidine (5-AzaC). Both of these drugs have been clinically proven to be well-tolerated and to have drug-sensitizing, quiescence-stabilizing, and apoptosis-inducing effects in cancer cells.
“We chose 5-AzaC because it could complement 6-MP’s effects on the transcriptome and epigenome, and—as indicated by many Phase 1 clinical trials—5-AzaC is well tolerated.”
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DOI - https://doi.org/10.18632/oncotarget.27922
Full text - https://www.oncotarget.com/article/27922/text/
Correspondence to - Anthony Lucci - alucci@mdanderson.org and Balraj Singh - bsingh@mdanderson.org
Keywords - resistant TNBC, minimal residual disease, intratumor heterogeneity, breast cancer relapse, metastasis prevention
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