Study Reveals New Treatment for Aggressive BRCA1-Deficient and Triple-Negative Breast Cancers
Triple-negative breast cancers (TNBC), make up 15% of all breast cancer diagnoses and are the most aggressive type of breast cancer due to their resistance to treatment. TNBC means that cancer tumor cells lack receptors for three key factors: estrogen, progesterone, and human epidermal growth factor 2 (HER2). Estrogen and progesterone are key hormones to reproductive health, while HER2 is a protein that ensures cells grow normally. These three factors typically guide breast cancer treatment. Since TNBC lacks the receptors for these factors, these treatments are ineffective and researchers are looking to find alternate approaches. Some TNBCs also have mutations in the BRCA1 gene (BReast CAncer gene 1), which is responsible for helping repair damaged DNA and preventing uncontrolled cell growth. When BRCA1 is defective, cells lose an important repair mechanism, making them more vulnerable to DNA-damaging agents and more likely to spread unchecked, leading to tumors. Cancer cases that are both triple negative and BRCA1 deficient are aggressive and are challenging to efficiently treat, often requiring an extensive cocktail of chemotherapy drugs to treat all aspects of the cancer. The recent study by Imene Tabet et al. investigated the use of the poison gemcitabine to treat triple-negative and BRCA1 deficient breast cancers to improve cancer outcomes.
The findings of the paper reveal that BRCA1-deficient TNBC cells have an increased sensitivity to gemcitabine when compared to BRCA1-positive cells. Gemcitabine is a chemotherapy drug that kills tumors by stopping DNA replication from taking place. In order for double stranded DNA to replicate, the two strands separate and each individual strand acts as a puzzle template to make new DNA. Each strand tries to complete itself by searching for its missing pieces from a pool of miscellaneous, solo puzzle pieces. Gemcitabine works by decreasing the amount of puzzle pieces available to complete the single stranded DNA puzzles. With no pieces to complete the puzzle, DNA cannot be replicated. If DNA is not replicated, then the cell cannot divide and the tumor cannot grow.
The findings of the paper reveal that BRCA1-deficient TNBC cells have an increased sensitivity to gemcitabine when compared to BRCA1-positive cells. Gemcitabine is a chemotherapy drug that kills tumors by stopping DNA replication from taking place. In order for double stranded DNA to replicate, the two strands separate and each individual strand acts as a puzzle template to make new DNA. Each strand tries to complete itself by searching for its missing pieces from a pool of miscellaneous, solo puzzle pieces. Gemcitabine works by decreasing the amount of puzzle pieces available to complete the single stranded DNA puzzles. With no pieces to complete the puzzle, DNA cannot be replicated. If DNA is not replicated, then the cell cannot divide and the tumor cannot grow.
Depiction of cells in development
Image Source: ColiN00B
Furthermore, the tumors that kept growing after treatment often had DNA damage due to the gemcitabine. This DNA damage led to the tumor cells being recognized as invaders by the immune system and targeted for destruction. If the gemcitabine did not kill the tumor, the patient’s own immune system would finish the job and destroy the tumor.
Overall, this study found that gemcitabine has potential as a therapy and treatment option for BRCA1-deficient TNBC by (1) preventing tumor cells from growing and spreading via preventing DNA replication and (2) targeting tumors to be destroyed by the patient’s own immune system. The results of this study serve to help experiences of patients with aggressive BRCA1-deficient TNBC cases by eliminating the need of an extensive cocktail of chemotherapy drugs and simplifying the cocktail to include potent gemcitabine.
Overall, this study found that gemcitabine has potential as a therapy and treatment option for BRCA1-deficient TNBC by (1) preventing tumor cells from growing and spreading via preventing DNA replication and (2) targeting tumors to be destroyed by the patient’s own immune system. The results of this study serve to help experiences of patients with aggressive BRCA1-deficient TNBC cases by eliminating the need of an extensive cocktail of chemotherapy drugs and simplifying the cocktail to include potent gemcitabine.
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