Pancreatic cancer: Only with 5% survival rate
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Pancreatic cancer: Only with 5% survival rate
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Pancreatic cancer: Only with 5% survival rate. Why is the treatment of pancreatic cancer so difficult? The incidence of pancreatic cancer is not high, but once you get the disease, it is often at an advanced stage.
At present, with the advancement of medical technology, the survival time of many major cancers has been greatly improved, but the 5-year survival rate of pancreatic cancer is still only about 5%.
Unpredictable ghost
The first difficulty of pancreatic cancer: it is difficult to find.
In September this year, Justice Ginsberg died at the age of 87 from complications of metastatic pancreatic cancer.
Ruth Bader Ginsburg (YouTube video screenshot)
Ginsberg was lucky. Since she had experienced bowel cancer before, regular follow-ups after bowel cancer treatment allowed her to detect pancreatic cancer early. The earlier cancer is discovered, the easier it is to treat, and even some types of cancer can be cured. After receiving timely surgical treatment, Ginsberg obtained a survival period of up to 11 years.
Other patients with pancreatic cancer are not so lucky, and most patients are often at an advanced stage when they are diagnosed.
What reasons cause this?
First of all, from the anatomical structure, the pancreas hides behind other organs, making it difficult to detect early pancreatic cancer during routine examinations (including general imaging examinations).
Secondly, pancreatic cancer is not a high-incidence cancer, and CT is not suitable for large-scale general screening.
In contrast, breast cancer has mammography, cervical cancer has smears, prostate cancer has PSA (prostate specific antigen) screening, and lung cancer has low-dose spiral CT screening for high-risk populations. These screenings make cancer Treatment can win at the starting line, greatly reducing the death rate of related cancers.
In addition, from the perspective of symptoms, pancreatic cancer is very good at disguising.
Early-stage pancreatic cancer has no obvious and specific symptoms. Patients often go to the hospital for “common manifestations” such as nausea, vomiting, abnormal bowel motility, fatigue, weakness, appetite changes, jaundice, back pain, and abnormal weight loss.
Because canceration affects pancreatic function, pancreatic cancer is often disguised as diabetes. Data shows that about 80% of pancreatic cancer patients have new diabetes or insulin intolerance at the time of diagnosis.
A 30-year follow-up study conducted by JAMA Oncology of 150,000 people in August this year showed that compared with the general population, people with diabetes and those with abnormal weight loss have an increased risk of pancreatic cancer. If you are newly diagnosed with diabetes and lose more than 8 pounds, the risk of pancreatic cancer can soar to 6.75 times.
Therefore, people with diabetes who have lost weight need to be especially vigilant about pancreatic cancer.
What is the difficulty in the treatment of advanced pancreatic cancer?
The second difficulty of pancreatic cancer: treatment is difficult.
Two therapies that are currently being researched in the field of tumor therapy: immunotherapy and targeted therapy, have encountered Waterloo in the field of pancreatic cancer.
The PD-1, PD-L1, and CTLA-4 that we usually mention are all “immune checkpoints”, and antibodies to these proteins are commonly referred to as immunotherapy. The mechanism is to relieve cancer cells from inhibiting immune cells, allowing Immune cells can kill cancer cells.
Generally speaking, if a certain cancer has more genetic mutations, the more suitable it is to use immunotherapy. Pancreatic cancer has mutations, but it is a desert of immune cells.
Even though K drugs and other immunotherapies can relieve the defenses of cancer cells, due to the lack of immune cell support, K drugs are only clever women who can’t cook without rice.
Anti-PD-1 K drugs and O drugs have been approved for more than 10 cancer indications, but there is no specific approval for the treatment of pancreatic cancer.
The latest failure case is the PD-L1 monoclonal antibody durvalumab combined with the CTLA-4 monoclonal antibody tremelimumab for the treatment of pancreatic cancer. In the phase 2 clinical trial, only 3.1% of patients had objective remission after treatment, and their performance was quite dismal. [5]
Look at targeted therapy again. At present, targeted therapy has brought great hope to many cancer patients, such as non-small cell lung cancer. If EGFR targeted drugs can be used, not only will the side effects be lower than chemotherapy, but the treatment effect will be very good.
The mechanism of action of targeted drugs is to target specific gene mutations of cancer cells, selectively kill cancer cells and reduce damage to normal cells.
Among them, gene mutations can be divided into driver mutations and non-driver mutations. Only the driver mutation is more important for the canceration of the driver cell. By targeting the driver mutation, there is the effect of catching the thief first.
On the contrary, if the mutation is not important for carcinogenicity, the effect of the targeted drug will become a chicken rib, and pancreatic cancer lacks such an important mutation as a suitable target.
In 2005, the US FDA approved the EGFR inhibitor erlotinib combined with gemcitabine for the treatment of advanced pancreatic cancer. In clinical trials, although this combination therapy statistically significantly improved the overall survival rate (OS) of patients, increasing the one-year survival rate from 17% to 23%, but the median survival time of patients was only compared with the control treatment Added 10 days.
New hope: how will the treatment of pancreatic cancer break?
Since the crux of pancreatic cancer is that there are too few immune cells, what if we can introduce immune cells into pancreatic cancer tissue to improve the treatment effect?
Well, this is indeed the current treatment idea.
One of the more promising drugs today is the CXCR4 agonist (BL-8040). CXCR4 is a receptor, and its ligand is CXCL12. The interaction between them is important for the regulation of pancreatic cancer tumor microenvironment.
We can compare BL-8040 to a “desert camel”, which is responsible for carrying immune cells into the immune desert of the pancreas: BL-8040 changes the tumor’s microenvironment by activating CXCR4 receptors, helping immune cells to enter pancreatic tissue more easily .
Clinical trials have shown that after treatment with “Desert Camel”, there are indeed more CD8+ effector T cells in the pancreatic tissue that can kill tumors. Not only that, but myeloid suppressor cells (MDSCs) and regulatory T cells (Treg) that suppress immunity were also reduced at the same time.
In this way, BL-8040 can be regarded as a good camel. It can not only pull in useful cells, but also pull messy cells out.
In a related phase 2 clinical trial (COMBAT clinical study), two treatment options were investigated for patients with uncontrollable advanced pancreatic cancer: BL-8040+K drug (abbreviated as non-chemotherapy regimen), BL-8040+K drug+ Chemotherapy (referred to as combined chemotherapy regimen). [6]
Thirty-seven patients received a non-chemotherapy regimen, and only one patient experienced partial remission. When this patient was enrolled, it had been more than 2 years since the initial diagnosis. He had six liver metastases and three retroperitoneal lymph nodes. The clinical trial was a third-line treatment.
After 7 weeks of non-chemotherapy treatment, the re-examination results showed a partial remission. At 4 months, the tumor lesion size was reduced by 39.7%, which is considered to be a significant effect. However, from the overall effect, the objective response rate of non-chemotherapy regimens is only 3.4%, and the median OS is 3.3 months.
However, for pancreatic cancer 2 to 3 line treatment, this effect has been quite good. If you analyze it carefully, the median OS of the second-line treatment is 7.5 months, which is not too bad. The main reason is that the effect of the third-line treatment is hindered.
In the combination chemotherapy regimen, the objective response rate reached 32%, and the mDOR (Endurance of Response) was 7.8 months, which was higher than that of the non-chemotherapy regimen overall.
Judging from this result, only the “desert camel” is not enough. K medicine is needed to relieve the resistance of cancer cells to immune cells, and the assistance of chemotherapy is also needed. Chemotherapy directly kills cancer cells, increases the release of new cancer antigens, facilitates CD8+ effector T cells to recognize targets, reduces immunosuppressive Treg cells, and enhances the lethality of CD8+ T cells.
Of course, this is only a phase 2 clinical result. Although it brings hope, strict controlled trials are needed to prove the efficacy of the combination therapy.
Only relying on a desert camel like CXCR4 agonist can hardly turn pancreatic cancer into an oasis of immune cells. We need more research to achieve the goal of truly greening the immune desert.
Pancreatic cancer: Only with 5% survival rate
(source:internet, reference only)
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