Pancreatic Cancer 5-Year Survival Rate Stagnates at 10%... Potential for Paradigm Shift with Development of K-RAS Targeted Therapies

Pancreatic cancer is often detected late and is frequently difficult to operate on at the time of diagnosis, causing the 5-year survival rate to remain at the 10% level. Despite recent advancements in anticancer treatment technologies, the reasons why pancreatic cancer survival rates have not significantly increased and the current status of the latest treatment research to overcome this have been revealed.

Reasons for Late Detection and Difficulty in Surgery

Professor Im Ga-ram, a specialist in Gastroenterology at Severance Hospital, cited two reasons for the delayed detection of pancreatic cancer. First, because the pancreas is located in the retroperitoneal area within the abdominal cavity, it is difficult to examine the pancreas in detail from the head to the tail using the abdominal ultrasound used in general health checkups. In particular, if there is a lot of fat or if the intestines are blocking the view, diagnosis is not easy without additional tests such as CT or MRI. Furthermore, pancreatic cancer progresses very rapidly, so even if there were no abnormalities in a test one year ago, it is often found in an advanced stage during the next checkup.

The possibility of surgery is also limited. Professor Im explained that according to reports worldwide, only about 10% to 20% of patients are eligible for early surgery. Since the pancreas often surrounds blood vessels coming from the aorta, cases where surgery is impossible are frequent, and the fact that it is difficult to confirm with imaging technology before the cancer cells reach a size of about 5mm (an accumulation of approximately 1 billion cancer cells) also acts as a challenge in diagnosis and treatment.

Causes of Low Survival Rates and Limitations of Combination Chemotherapy

The 5-year survival rate of pancreatic cancer has remained at the current 10% level, compared to approximately 4–5% when single anticancer drugs were used in 1999. Professor Im pointed to the thick fibrotic tissue surrounding pancreatic cancer as the cause of this stagnation. Pancreatic cancer has an unusually high amount of fibrotic tissue in its vicinity, and this tissue prevents immune cells from invading the center of the cancer cells, resulting in reducing the response rate of immune checkpoint inhibitors to nearly 0%. Additionally, the biological characteristic where resistance develops early within the pancreatic cancer itself makes treatment difficult.

Combination chemotherapies currently used as standard treatments, such as FOLFIRINOX (a combination of three drugs) or Gemstarbin and Abraxane (a combination of two drugs), have the effect of extending survival by about 3 to 6 months compared to the use of a single drug. However, Professor Im stated that because multiple drugs are used simultaneously, the risk of side effects increases, and since the expected extension of life span is not long, there are difficulties in treating elderly patients.

Status of K-RAS Mutation Targeted Therapy Development

The field gaining attention as a new mutation for pancreatic cancer treatment is K-RAS targeted therapy. The K-RAS mutation, found in approximately 90–95% of pancreatic cancer patients, was previously considered impossible to develop drugs for due to its "smooth ball-like" structure that lacked a site for drugs to bind. However, research accelerated after a binding site was discovered about 10 years ago.

Currently, drugs approved by the FDA apply only to specific sub-types (1–2%), but recently, it was reported that a drug called Daraksolasibi extended the survival period of patients by about twice the amount in a Phase 2 clinical trial. Based on these research results, Professor Im predicted that targeted therapies that can be used in clinical practice will emerge soon. Professor Im mentioned cases where patients continue healthy treatment for more than 3 to 4 years even with systemic metastasis, and emphasized that pancreatic cancer patients should not give up on treatment and must fight.