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An overview of the past decade of bufalin in the treatment of refractory and drug-resistant cancers: current status, challenges, and future perspectives

Profound progress has been made in cancer treatment in the past three decades. However, drug resistance remains prevalent and a critical challenge. Drug resistance can be attributed to oncogenes mutations, activated defensive mechanisms, ATP-bind cassette transporters overexpression, cancer stem cells, etc. Chinese traditional medicine toad venom has been used for centuries for different diseases, including resistant cancers. Bufalin is one of the bufadienolides in toad venom that has been extensively studied for its potential in refractory and drug-resistant cancer treatments in vitro and in vivo. In this work, we would like to critically review the progress made in the past decade (2013-2022) of bufalin in overcoming drug resistance in cancers. Generally, bufalin shows high potential in killing certain refractory and resistant cancer cells via multiple mechanisms. More importantly, bufalin can work as a chemo-sensitizer that enhances the sensitivity of certain conventional and targeted therapies at low concentrations. In addition, the development of bufalin derivatives was also briefly summarized and discussed. We also analyzed the obstacles and challenges and provided possible solutions for future perspectives. We hope that the collective information may help evoke more effort for more in-depth studies and evaluation of bufalin in both lab and possible clinical trials.

 

Comments:

It's evident from your description that bufalin, a compound found in toad venom, has shown promising potential in overcoming drug resistance in cancer cells. The research you outlined highlights several key points:

1. **Multiple Mechanisms of Action:** Bufalin has demonstrated its ability to kill certain refractory and resistant cancer cells through various mechanisms. Understanding these mechanisms is crucial in developing targeted therapies.

2. **Chemo-Sensitizing Effect:** Bufalin acts as a chemo-sensitizer, enhancing the sensitivity of certain conventional and targeted cancer therapies at low concentrations. This property is valuable in combination therapies, where it can enhance the efficacy of existing treatments.

3. **Derivative Development:** The development of bufalin derivatives indicates ongoing efforts to optimize its properties for better efficacy and reduced side effects. This is a common strategy in drug development to enhance the therapeutic potential of natural compounds.

4. **Obstacles and Challenges:** Acknowledging the obstacles and challenges is important for refining research strategies. Identifying and addressing issues related to bufalin's stability, delivery methods, and potential side effects are crucial for its successful translation into clinical applications.

5. **Future Perspectives:** Providing possible solutions for future research and clinical trials suggests a proactive approach. Addressing the identified challenges, exploring new delivery mechanisms, and conducting in-depth studies are essential steps for advancing bufalin research.

This summary not only highlights the progress made in bufalin research but also emphasizes the importance of continued studies and clinical trials. The potential of bufalin in overcoming drug resistance in cancer cells could significantly impact cancer treatment strategies, offering hope for patients with refractory and resistant cancers. Researchers and clinicians can use this information as a foundation for further exploration and development of bufalin-based therapies.

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S7821 Bufalin Bufalin (BF) is a potent inhibitor of steroid receptor coactivator SRC-3, SRC-1 and Na+/K+-ATPase. Bufalin binds to the subunit α1, α2 and α3 of Na+/K+-ATPase with Kd of 42.5 nM, 45 nM and 40 nM, respectively. Bufalin is a major immunoreactive component isolated from the Chinese medicine Chan Su with anti-cancer activity.

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