Breakthrough Treatment: How Mebendazole Boosts Radiation Therapy For TNBC

This article discusses two studies showing the potential use of mebendazole to make radiation treatment of triple-negative breast cancer more effective.

Contents hide

1 Why Triple-Negative Breast Cancers are Hard to Treat

2 Mebendazole Enhances Radiation Therapy in Triple-Negative Breast Cancer

2.1 Mebendazole Effect on TNBCs

3 Enhancing Natural Killer Cell Activity with MBZ + RT

3.1 Key Findings

4 The Potential of Mebendazole in TNBC Treatment

Why Triple-Negative Breast Cancers are Hard to Treat

Triple-negative breast cancer (TNBC) is one of the most aggressive and difficult-to-treat subtypes of breast cancer.

Unlike other types, TNBC lacks the three primary receptors:

Therapies typically target these receptors.

This absence leaves patients with limited treatment options, relying heavily on chemotherapy, surgery, and radiation therapy (RT).

While radiation therapy is a critical component of TNBC treatment, it often falls short due to the emergence of therapy-resistant cancer cells.

These resistant cells contribute to tumor recurrence and progression, presenting a significant hurdle in achieving long-term control of TNBC.

Recent research has explored the potential of repurposing existing drugs to enhance the efficacy of radiation therapy.

One promising candidate is mebendazole (MBZ), a well-known anti-parasitic drug that has demonstrated anti-cancer properties.

Two key studies highlight how MBZ can improve the effectiveness of RT in treating TNBC and overcoming radiation resistance.

Mebendazole Enhances Radiation Therapy in Triple-Negative Breast Cancer

A groundbreaking study by Zhang et al. in 2019 evaluated the role of MBZ in enhancing radiation therapy for TNBC.[1]

The research addressed a critical issue: Radiation therapy not only kills cancer cells but also reprograms some surviving cells into breast cancer-initiating cells (BCICs).

These BCICs are highly resistant to therapy and drive recurrence and metastasis.

Mebendazole Effect on TNBCs

Depletion of BCICs: MBZ effectively reduced the pool of breast cancer-initiating cells and prevented the radiation-induced reprogramming of cancer cells into BCICs.
Cell Cycle Arrest and DNA Damage: MBZ arrested TNBC cells in the G2/M phase of the cell cycle, a point where cells are most sensitive to radiation. It also caused double-strand breaks in DNA and triggered apoptosis (programmed cell death), enhancing the destructive effects of RT.
Improved Tumor Control: In a human TNBC xenograft model, MBZ combined with RT significantly improved tumor control compared to RT alone.

Conclusion: This study supports using mebendazole as an adjunct to radiation therapy in triple-negative breast cancer, as it prevents the emergence of therapy-resistant cancer cells and amplifies the overall efficacy of radiation treatment.

Enhancing Natural Killer Cell Activity with MBZ + RT

In a more recent study, Choi et al. (2022) investigated how MBZ enhances the anticancer effects of RT, particularly in TNBC cells resistant to radiation therapy.[2]

The research delved into the synergistic effects of MBZ and RT and uncovered additional mechanisms through which MBZ contributes to tumor control.

Key Findings

Increased Natural Killer (NK) Cell Activity: Combining MBZ and RT boosted NK cell-mediated cytotoxicity, a natural immune response that targets and destroys cancer cells.
Enhanced DNA Damage: Similar to Zhang et al., this study found that MBZ caused DNA double-strand breaks, significantly damaging cancer cells.
Cell Cycle Blockade: MBZ blocked cell cycle progression, making cancer cells more vulnerable to the effects of radiation.
Reduced Metastasis: In mouse models, the combined treatment decreased tumor volume and the number of lung metastases without causing additional liver or kidney toxicity.

Conclusion: The findings suggest that MBZ sensitizes TNBC cells to radiation and enhances the body’s immune response against the cancer, offering a dual approach to combating radiation resistance.

The Potential of Mebendazole in TNBC Treatment

Together, these studies highlight the potential of MBZ as a powerful addition to radiation therapy in TNBC.

By depleting therapy-resistant cancer cells, inducing DNA damage, and boosting immune responses, MBZ addresses multiple challenges associated with TNBC treatment.

Notably, both studies demonstrated that MBZ does not increase toxicity, making it a safe and compelling candidate for combination therapy.

Moving Forward

The repurposing of mebendazole for cancer treatment could be a game-changer for patients with TNBC. While further clinical trials are needed to confirm these findings in larger populations, the evidence is promising.

Combining MBZ with radiation therapy offers new hope in the fight against one of the most aggressive forms of breast cancer, potentially improving outcomes and saving lives.

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References:

Zhang L, Bochkur Dratver M, Yazal T, Dong K, Nguyen A, Yu G, Dao A, Bochkur Dratver M, Duhachek-Muggy S, Bhat K, Alli C, Pajonk F, Vlashi E. Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer. Int J Radiat Oncol Biol Phys. 2019 Jan 1;103(1):195-207. doi: 10.1016/j.ijrobp.2018.08.046. Epub 2018 Sep 7. PMID: 30196056; PMCID: PMC6457649.
Choi HS, Ko YS, Jin H, Kang KM, Ha IB, Jeong H, Lee JH, Jeong BK, Kim HJ. Mebendazole Increases Anticancer Activity of Radiotherapy in Radiotherapy-Resistant Triple-Negative Breast Cancer Cells by Enhancing Natural Killer Cell-Mediated Cytotoxicity. Int J Mol Sci. 2022 Dec 7;23(24):15493. doi: 10.3390/ijms232415493. PMID: 36555137; PMCID: PMC9779603.

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