Triple-Negative Breast Cancer Treatment: A Two-Front Treatment

Triple-Negative Breast Cancer Treatment: A Two-Front Treatment ...

Researchers at Baylor College of Medicine and collaborating institutions have identified a combination therapy for treating triple-negative breast cancer (TNBC), which has resulted in long-term tumor regression in an animal model of the disease.

On two fronts, the chemotherapy drug cyclophosphamide eliminated tumor cells, while on the other side, another medication inhibited tumor-associated cells called macrophages, which block the body''s immune response against the tumor. This two-front strategy effectively treated several highly aggressive TNBC primary tumors and metastasis. The findings were published in the journalCancer Research.

TNBC is a widespread subtype of breast cancer with a greater prognosis than other breast cancer subtypes, according to co-corresponding authorDr. Jeffrey Rosen, Distinguished Service Professor of molecular and cellular biology at Baylor.

Animal models had previously shown that, although treating the tumors with cyclophosphamide initially eliminated the cancer, the disease came back eventually. A closer examination of the tumor microenvironment revealed that the tumors that returned had typically several macrophages.

The authors of this paper and a student in the Baylorsgraduate school of biomedical sciences working together in the Rosen and Zhang laboratories found that eliminating macrophages with either a small molecule inhibitor or a monoclonal antibody towards CSF1R, a marker on these cells, were discussed.

The cancer patients were treated with a combination of medicines for several months. Eventually, they stopped treating and monitored the progression of tumors in the treated animals.

Singh said the findings were positive. Typically, a month after discontinuing the single-drug treatment, the tumors returned. We were pleased to discover that the tumors did not return a month after discontinuing the combination therapy. In two animal models of TNBC, we observed a strong response.

Animals with a strong response were able to prevent new tumors from developing. We challenged these animals with fresh tumor cells, and 40% of them rejected them. This indicated that the animals had an immune system capable of resolving new tumor growth. We also treated lung tumor metastasis with combination therapy, which also exacerbated cancer growth.

With a sustained response, Rosen and his colleagues examined how the tumor microenvironment had improved in the animals.

Xiang H.F. Zhang, the interim director of the Lester and Sue Smith Breast Center, and William T. Butler, a doctor at Baylor University, confirmed that when we treated the tumors with one of the two drugs, which did not produce a long-term response, immune B and T cells involved in the treatment of the tumor did not enter it, and that they remained in the periphery of the tumor mass, according to Zhang. Zhang, also a member of the Dan L Duncan Comprehensive Cancer

Both B and T cells were found in the tumor tissue after combination therapy, suggesting that they were interacted to minimize tumor elimination in a secure manner.

Researchers studied whether the macrophage signature they had observed in animal models was present in TNBC from patients. Indeed, tumors from patients with the worse diagnosis also showed a large number of macrophages, according to Rosen. This signature might bolster our knowledge of potential combination therapy patients.

The researchers are planning to conduct a clinical study to investigate the significance of their technique in treating human TNBC.

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