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The mystery of the KRAS gene: Why can this small gene change the fate of cancer?
KRAS gene, this small gene plays a vital role in cancer research. It provides instructions for making the K-Ras protein, which is part of the RAS/MAPK signaling pathway and is able to transmit signals from outside the cell to the cell nucleus. This signal can instruct cells to grow, divide, or mature. KRAS was originally identified from the Kirsten rat sarcoma virus, hence the name. When it is present in the cell's genome, it is called a proto-oncogene and is strongly expressed in many cancer types.
The KRAS gene is a GTPase that converts guanosine triphosphate (GTP) into guanosine diphosphate (GDP), a process that effectively turns the K-Ras protein on and off.
KRAS Function
KRAS acts as a molecular switch of cells, controlling the transmission of various cell signals. When KRAS binds to GTP, it becomes activated and recruits other important signaling proteins, such as c-Raf and PI3-kinase. Abnormalities in this process can lead to the development of tumors, especially in patients with certain cancers (such as lung, breast, and colon cancer).
Clinical significance: mutations and cancer
KRAS mutations are associated with the development of a variety of malignancies, including lung adenocarcinoma, pancreatic cancer, and colorectal cancer. These mutations are often caused by single amino acid or nucleotide substitutions, leading to abnormal activation of the KRAS protein. In colorectal cancer specifically, mutations in KRAS affect how patients respond to specific treatments, such as EGFR inhibitors.
In colorectal cancer, KRAS mutations can predict low response rates to anticancer drugs such as Cetuximab and Panitumumab, affecting treatment selection.
KRAS association with different types of cancer
Colorectal cancerIn colorectal cancer, the sequence in which KRAS mutations occur is critical. In general, KRAS mutations can cause tumors to become more aggressive from benign lesions, especially when they occur after APC mutations. These mutations significantly affect the patient's treatment outcome and prognosis.
Lung cancer
The presence of KRAS mutations in lung cancer patients is usually mutually exclusive with EGFR mutations. Studies have shown that the response rate to EGFR inhibitors in patients with KRAS mutations is less than 5%. These mutations not only affect the expression of KRAS, but also the expression of other related genes, thereby further affecting the patient's prognosis.
Pancreatic cancerIn pancreatic ductal adenocarcinoma, KRAS mutations are present in more than 90% of cases. Although Sotorasib is the only drug approved for KRAS G12C mutation on the market, there is currently a lack of effective drugs for G12D mutation.
KRAS detection
As our understanding of KRAS mutations deepens, KRAS testing becomes increasingly important, especially in treatment decisions for patients with colorectal cancer. The FDA has approved several tests to help doctors identify patients who may benefit from treatment with EGFR inhibitors.
Potential as a therapeutic target
Due to the key role of KRAS mutations in many cancers, it has become an important therapeutic target. However, drug development for KRAS is constrained by the high affinity of GTP and GDP, making the development of small molecule inhibitors challenging.
The KRAS G12C mutation has promoted the development of new inhibitors, such as the successful approval of Sotorasib, which indicates the therapeutic potential of KRAS as a target.
As cancer research continues to deepen, the role of the KRAS gene has received more and more attention. It is not just a single gene mutation, but a key factor that affects the fate of many cancers. So, are we ready for a new round of cancer treatment revolution led by KRAS?
