(Health Korea News / Lee Chung-man) Expectations are growing that PARP or KRAS inhibitors could become a new targeted treatment for pancreatic cancer, which is known to be an incurable disease.
Pancreatic cancer has a very low survival rate among cancers. According to statistical data from the Central Cancer Registry, the survival rate of pancreatic cancer is only 13.9% as of 2019.
The reason the survival rate of pancreatic cancer is so low is because it metastasizes very quickly and there is no effective treatment yet. The most effective treatment for pancreatic cancer is surgical resection, but surgery is known to be possible for only about 20% of all patients.
For unresectable pancreatic cancer, chemotherapy followed by radiation therapy may be considered. However, the 5-year survival rate for patients with unresectable pancreatic cancer is only 6%. This is why pancreatic cancer is recognized as an incurable disease.
In addition, because chemoradiotherapy drastically reduces the patient’s quality of life due to cytotoxic side effects, there is a tendency not to actively administer the treatment. Since they cannot survive for a long time anyway, the focus is on moderately suppressing the progression of cancer, improving the patient’s symptoms, and improving the quality of life.
Even the immunotherapy drugs that are popular these days are useless against pancreatic cancer. Pancreatic cancer is a representative non-immune tumor (cold tumor), and immune cells around the cancer tissue are extremely rare, making immune anti-cancer drugs ineffective.
So the drugs that are attracting attention these days are PARP or KRAS inhibitors.
At the American Association for Cancer Research (AACR) held in Boston from September 15 to 18, Dr. Eileen O’Reilly from the Pancreatic Cancer Research Center at Memorial Sloan Kettering Cancer Center (MSKCC) gave a presentation on pancreatic cancer treatment. We shared the latest knowledge.
At this event, Dr. O’Reilly’s research team announced the interim results of a phase 2 clinical trial evaluating the combination of Abbvie’s PARP inhibitor ‘veliparib’ and chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC). .
According to Dr. O’Reilly, the combination therapy failed to improve progression-free survival or overall survival compared to chemotherapy alone, but showed a better overall response rate. This is noteworthy because it shows that there is a correlation between PARP inhibitors and pancreatic cancer. The research team said, “It is known that approximately 5% of all pancreatic cancers overexpress BRCA1 and BRCA2, proteins that repair DNA. Using PARP inhibitors, pancreatic cancer can be treated by inhibiting BRCA1 and BRCA2.”
The drugs that have attracted more attention than PARP are KRAS inhibitors. KRAS is a type of RAS protein family involved in cell growth and differentiation, and KRAS mutations are found in many types of cancer.
In particular, as it is estimated that 80-90% of pancreatic cancers have KRAS mutations, expectations are growing that KRAS inhibitors could be a promising target treatment for pancreatic cancer.
Of course, there are still no approved KRAS inhibitors. ▲Amgen’s ‘Lumakras’ (ingredient name: sotorasib) and ▲BMS’ ‘Krazati’ (ingredient name: agdagrasib) received FDA approval and are now available to patients. is being used for. However, these drugs have clear limitations in that they can only target the G12C mutation, a subtype of the KRAS protein. G12C was developed so quickly because it is the most structurally understandable subtype of the KRAS mutations discovered to date.
Therefore, medical scientists and researchers in the biopharmaceutical industry are working to develop KRAS inhibitors or drugs that target the entire RAS protein group.
In fact, Revolution Medicines, an American bio venture company, began a phase 1 clinical trial in February this year to evaluate its multiple RAS inhibitor candidate ‘RMC-6236’ targeting patients with various types of RAS-mutated solid tumors. According to the company, pancreatic cancer patients treated with ‘RMC-6236’ improved progression-free survival and overall survival.
Dr. O’Reilly said, “KRAS inhibitors that can target not only G12C but also various mutations, or inhibitors that target the entire RAS protein family, will present a new method of treating pancreatic cancer.” He added, “Pancreatic cancer treatment is clearly facing a new paradigm shift.” . “New targeted treatments for pancreatic cancer will emerge within the next few years,” he predicted.
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