Some genetic mutations may improve survival rates

of pancreas It is located in the upper left part of the abdomen, behind the stomach.

As part of the digestive system, the pancreas produces enzymes used to break down food and also insulin to help maintain a person's health Blood glucose level Stable.

Pancreatic ductal adenocarcinoma begins in the cells that line the ducts of the pancreas.

Pancreatic cancer is one of the most difficult to find In the early stages, most people have no symptoms and the location of the pancreas makes it difficult to detect the tumor.

Treatment for pancreatic cancer depends on the stage of the cancer. If the cancer has not spread to other areas of the body, surgery It might be possible.

According to past research, in the later stages traditional cancer treatment Because it is not effective against pancreatic ductal adenocarcinoma, new treatment.

According to Dr. Zhao, the Kirsten rat sarcoma virus oncogene homologue (KRAS) gene was first isolated from cancer cell lines more than 30 years ago.

In a healthy environment, the KRAS gene plays an important role in cell growth and turnover. However, when the KRAS gene mutates, cancer cells can begin to grow and spread.

“The protein it encodes is GTPasehas enzymatic activity to convert. GTP vs. GDP and induce downstream signaling,” she explained.

“The KRAS gene has the most mutations. cancer gene In cancer, it causes activation of signal transduction pathways, promotes cancer cell proliferation, and suppresses cancer immunity,” Dr. Zhao said.

In addition to pancreatic cancer, previous studies have found KRAS mutations in:

For this study, Dr. Zhao and her team analyzed data from 803 people with pancreatic ductal adenocarcinoma.

Researchers found that study participants had the following symptoms: KRAS wild type And those with KRAS G12R mutations had better survival than those with KRAS G12D or KRAS Q61 mutations.

Additionally, scientists found that KRAS G12D mutations are correlated with metastatic disease and KRAS G12R mutations are common in well-to-moderately differentiated tumors.

“The results are not surprising,” Dr. Zhao said. “They are consistent with findings in other types of cancer and the biochemical characteristics of different KRAS mutation subtypes.”

“KRAS G12R is most prevalent in pancreatic ductal adenocarcinoma (about 15%), but rare in other cancers (about 1%),” she continued.

“The KRAS G12R mutation is known to cause cancers to grow less easily in traditional mouse models. Laboratory studies have shown that the KRAS G12R mutant has a different downstream signaling pathway, and the KRAS Q61 mutant is more oncogenic. This study is one of the first and largest in patients with pancreatic cancer to elucidate the molecular and clinical characteristics of KRAS-mutant pancreatic ductal adenocarcinoma.”

— Dr. Dan Zhao, study co-lead author

Dr. Zhao said KRAS was difficult to target until its recent discovery. KRAS G12C inhibitor.

“Currently, two KRAS G12C inhibitors – Sotrasif and higher dose — Approved by the US FDA. Lung cancer treatmentBut we don’t have it yet in pancreatic ductal adenocarcinoma,” she added.

In addition to this study, Dr. Zhao is also the principal investigator on the following studies: clinical trial This could provide further information about the safety and efficacy of adaglasib monotherapy in pancreatic ductal adenocarcinoma, she said.

“We hope that the results of this study will aid in the development of KRAS-targeted therapies and guide future combination therapy strategies targeting KRAS,” she added.

KRAS G12C inhibitors are currently undergoing research with potential. cancer vaccine.

For example, earlier this year, results from the following Phase 1 clinical trials were announced: ELI-002 This potential vaccine for colorectal and pancreatic cancer has shown that it may help prevent cancer recurrence in people who have already been treated for cancer.

“The current data is pancreatic cancer vaccine Phase 1 clinical trials are exciting,” said Dr. Zhao. “We look forward to seeing results in more patients soon in Phase 2 trials, especially in randomized controlled trials.”

MNT I also talked to AS Dr. Anton Bilchiksaid of the study, surgical oncologist, medical director, and director of the gastrointestinal-hepatobiliary program at Providence St. John's Cancer Institute in Santa Monica, California.

Dr. Bilchik said the study was critical because pancreatic cancer is a deadly disease, but little progress has been made in extending survival over the past 20 years.

“KRAS is a very important target for vaccines,” he continued. “I think one of the problems is that we don't know how long the effects will last because some people speculate that the effects of vaccine therapy may only last for a very short time.” There are many different subtypes, so we're trying to learn which specific subtypes are most important to target.”

“So there’s still a lot of work to do, but it’s definitely very exciting. immunotherapy or vaccine therapy has so far shown to be beneficial in pancreatic cancer,” Dr. Bilchik said.