Treatment of Anticancer-Resistant Metastatic Cancer
- Researchers have developed novel compounds that show potential in combating metastatic cancer that has become resistant to conventional anticancer drugs, while also minimizing teh risk of side effects.
- A study published in the British Journal of Pharmacology details the work of Park Ki-cheong, a surgery professor at Yonsei University College of Medicine, and Kim Seok-mo, leading...
- Metastatic cancer often develops resistance to existing chemotherapy treatments, reducing their effectiveness. The study found that suppressing the SERCA protein function in metastatic cancer cells enhances the therapeutic...
New Compounds Show Promise Against Drug-Resistant Metastatic Cancer
Table of Contents
- New Compounds Show Promise Against Drug-Resistant Metastatic Cancer
- New Compounds Show Promise Against Drug-Resistant Metastatic Cancer: Q&A
- What is the Good News About New Cancer Treatments?
- What is Metastatic Cancer?
- How Do the New Compounds Work?
- What is the SERCA Protein, and Why is it Critically important in Cancer Treatment?
- Who Led the Research on These New Compounds?
- What Were the Key Findings of the Study?
- How Did the Researchers Develop Compounds That Target SERCA 1 Selectively?
- What Were the Results of the Mouse Study?
- What is the Significance of Reducing Heart Disease Risk?
- How do CKP 1 and CKP 2 compare with older compounds?
- What are the Next Steps for This Research?
Researchers have developed novel compounds that show potential in combating metastatic cancer that has become resistant to conventional anticancer drugs, while also minimizing teh risk of side effects.
Targeting SERCA Protein for Cancer Treatment
A study published in the British Journal of Pharmacology details the work of Park Ki-cheong, a surgery professor at Yonsei University College of Medicine, and Kim Seok-mo, leading a research team at Gangnam Severance Hospital. Their research focused on cancer cell tissues from patients with drug-resistant metastatic cancers. The team discovered that inhibiting the SERCA protein, which plays a role in calcium ion transport within cells, could effectively suppress cancer cell growth in mice.
Overcoming Chemotherapy Resistance
Metastatic cancer often develops resistance to existing chemotherapy treatments, reducing their effectiveness. The study found that suppressing the SERCA protein function in metastatic cancer cells enhances the therapeutic effect of anticancer drugs. Though, previous SERCA protein inhibitors carried an increased risk of heart disease as a side effect.
Selective Inhibition of SERCA 1
The researchers concentrated on the different subtypes of the SERCA protein, noting that SERCA 2 is crucial for heart muscle function. they developed selective inhibitors, CKP 1 and CKP 2, specifically targeting SERCA 1, which is linked to anticancer resistance. This selective targeting aims to avoid the heart-related side effects associated with earlier inhibitors.
Mouse Study Results
To evaluate the effectiveness of CKP 1 and CKP 2, researchers conducted experiments on mice. They compared the new compounds with existing anticancer drugs, sorafenib and Renvatinib. Cancer cells exhibiting resistance were isolated from metastatic cancer patient tissues and showed increased SERCA 1 protein levels. The results indicated that combining CKP 1 or CKP 2 with either sorafenib or Renvatinib significantly suppressed tumor growth. Importantly, no heart disease side effects were observed in the mice.
Reduced Heart Disease Risk
Further tests were conducted to assess the potential for heart-related side effects. Mice were administered Top Sigargin, an existing SERCA inhibitor, as well as the new CKP 1 and CKP 2 compounds. Approximately 30% of the mice treated with top Sigargin died, while no deaths occurred in the groups receiving CKP 1 and CKP 2. The researchers attribute this to the selective action of CKP 1 and CKP 2, which impede SERCA 1 function while preserving SERCA 2 function, thus avoiding heart disease side effects.
Future Implications
According to Kim Seok-mo, the study has led to “a drug that can treat the anticancer drugs that are resistant to existing anticancer drugs, and also the side effects of heart disease.” Park Ki-cheong added that the research,which has been patented both domestically and internationally,”will lead to a follow -up study for future clinical and new drug advancement.”
New Compounds Show Promise Against Drug-Resistant Metastatic Cancer: Q&A
What is the Good News About New Cancer Treatments?
Researchers have developed new compounds with promising results in combating metastatic cancer that has become resistant to conventional chemotherapy. These new compounds also aim to minimize the risk of side effects.
What is Metastatic Cancer?
Metastatic cancer is cancer that has spread from its original location to other parts of the body. this makes it more difficult to treat.
How Do the New Compounds Work?
These new compounds target the SERCA protein, specifically SERCA 1, which plays a role in cancer cell growth and drug resistance. By inhibiting SERCA 1, the compounds can suppress cancer cell growth and enhance the effectiveness of existing anticancer drugs.
What is the SERCA Protein, and Why is it Critically important in Cancer Treatment?
SERCA (Sarco/Endoplasmic Reticulum Calcium ATPase) is a protein involved in transporting calcium ions within cells. In cancer cells, SERCA 1 is frequently enough linked to drug resistance. Inhibiting this protein can help overcome this resistance.
Who Led the Research on These New Compounds?
The research was led by Park Ki-cheong, a surgery professor at Yonsei University College of Medicine, and Kim Seok-mo, leading a research team at Gangnam Severance Hospital.
What Were the Key Findings of the Study?
The study found that inhibiting SERCA 1 could:
Suppress cancer cell growth in mice.
Enhance the therapeutic effect of existing anticancer drugs.
avoid heart-related side effects, a problem associated with some previous SERCA inhibitors.
How Did the Researchers Develop Compounds That Target SERCA 1 Selectively?
The researchers understood that different subtypes of the SERCA protein exist.They designed selective inhibitors, CKP 1 and CKP 2, to target only SERCA 1, which is linked to cancer resistance, and avoid impacting SERCA 2, which is crucial for heart muscle function.
What Were the Results of the Mouse Study?
The effectiveness of CKP 1 and CKP 2 was tested on mice. The results showed that:
Combining CKP 1 or CKP 2 with the existing anticancer drugs sorafenib or Renvatinib significantly suppressed tumor growth.
No heart disease side effects were observed in the mice treated with CKP 1 or CKP 2.
In contrast, a previous SERCA inhibitor, Top Sigargin, resulted in approximately 30% mortality in the mice.
What is the Significance of Reducing Heart Disease Risk?
Previous SERCA inhibitors have been associated with an increased risk of heart disease as a side effect. The new compounds,CKP 1 and CKP 2,selectively target SERCA 1 while sparing SERCA 2,which is critical for heart muscle function. This selective action significantly reduces the risk of heart-related side effects.
How do CKP 1 and CKP 2 compare with older compounds?
| Feature | CKP 1/CKP 2 | Older SERCA Inhibitors (e.g., Top Sigargin) |
|———————-|—————————————————————–|———————————————|
| Target | SERCA 1 (selective) | Non-selective, often affecting SERCA 2 |
| Heart Side Effects | Significantly reduced; no deaths in mouse studies | Higher risk; ~30% mortality in mouse studies|
| efficacy | Suppresses tumor growth with existing drugs | May have reduced efficacy due to side effects |
| Impact on SERCA 2 | Preserves SERCA 2 function, protecting heart health | Often inhibits SERCA 2, causing heart issues |
What are the Next Steps for This Research?
The research has been patented both domestically and internationally. According to Kim Seok-mo, the study has led to “a drug that can treat the anticancer drugs that are resistant to existing anticancer drugs and also the side effects of heart disease.” The researchers plan a follow-up study for future clinical and new drug advancements.