October is observed as Breast Cancer Awareness Month worldwide and we all know that early detection is crucial for curing cancer. As a renowned slogan reminds us, “Cancer is Curable if Detected Early.” Thus, better awareness of signs and symptoms and early diagnosis significantly enhance the prospects of successful breast cancer treatment.
But did you know that sometimes, after chemotherapy, some sneaky cancer cells go into hiding and then come back to cause trouble later on? These sneaky cancer cells are referred to as “dormant tumor cells” which imposes a big challenge for clinicians and scientists .
What are dormant tumor cells?
Chemotherapy is a powerful treatment that works well against rapidly dividing cancer cells, although it may be less effective against dormant cells that temporarily cease division. These dormant cells can remain non-dividing for years or even decades. Eventually, they can reactivate, contributing to cancer recurrence. This is why some cancer patients experience a recurrence of the disease years after completing chemotherapy. The resilience of these dormant cells presents a formidable challenge for both oncologists and researchers.
Fortunately, researchers have made a breakthrough by identifying a protein called P-glycoprotein commonly found in these cells. If we can inhibit the functioning of this protein, it could potentially make these hidden cells susceptible to chemotherapy or these hidden cells being destroyed by chemotherapy. Subsequently, preventing them from coming back and spreading to other parts of the body .
How does blocking P-glycoprotein help?
Well, resistance to therapy remains a significant hurdle in effectively treating metastatic breast cancer. Sometimes, cancer cells become resistant to treatment, making it difficult to kill them. P-glycoprotein plays a role in this resistance by keeping chemotherapy drugs from reaching the cancer cells effectively.
Acquiring multidrug resistance often involves the overexpression of drug transporters like P-glycoprotein, which keeps levels of chemotherapeutic drugs below the threshold needed to kill cancer cells. Overexpression of P-glycoprotein has been commonly observed in drug-resistant cell lines, especially after exposure to increasing concentrations of cytotoxic drugs. This phenomenon is well-documented in various cancers, such as hematological malignancies, sarcomas, breast cancer, and other solid tumors, often associated with poor clinical responses to chemotherapy [2,3].
Excitingly, a breakthrough has been made in the effort to address dormant tumor cells that tolerate chemotherapy. In an experiment on mice with breast cancer, scientists conducted a study to test the effectiveness of combining P-glycoprotein inhibitors with chemotherapy. The findings showed potential as the mice that received both treatments lived longer compared to those who only underwent chemotherapy. This suggests that incorporating P-glycoprotein inhibitors during treatment intervals could potentially benefit patients without adding more side effects from chemotherapy .
What could this discovery mean for breast cancer patients?
These findings hold great promise, suggesting that P-glycoprotein inhibitors may introduce a novel and effective approach to the treatment of breast cancer patients. The potential implications of this discovery are as follows:
This breakthrough offers a more effective way to combat drug-tolerant cancer cells, reducing the risk of cancer recurrence.
By inhibiting P-Glycoprotein, it might be possible to overcome drug resistance in cancer cells, improving the overall success of breast cancer treatment.
Ultimately, this could lead to better survival rates for breast cancer patients [2,3].
The final frontier
The inhibition of P-glycoprotein to target hidden, drug-resistant breast cancer cells is a significant breakthrough. It offers hope to breast cancer patients by providing a new way to fight drug resistance and improve treatment outcomes. However, the translation of these findings into clinical practice requires further research.
1. Sathishkumar, K. et al. 'Cancer incidence estimates for 2022 & projection for 2025: Result from National Cancer Registry Programme, India'. Indian J Med Res. (2022) 156(4–5), 598–607. DOI: 10.4103/ijmr.ijmr_1821_22.
2. Szebényi, K. et al. 'Effective targeting of breast cancer by the inhibition of P-glycoprotein mediated removal of toxic lipid peroxidation byproducts from drug tolerant persister cells'. Drug Resist Updat. (2023) 71, 101007. DOI: 10.1016/j.drup.2023.101007.
3. Pilotto Heming, C. et al. 'P-glycoprotein and cancer: what do we currently know?'. Heliyon. (2022) 8(10), e11171. DOI: 10.1016/j.heliyon.2022.e11171.