MON-322 - Administration of Inclisiran Sodium Is A Tumor-Biologically Beneficial Treatment for Cancer-Associated Hyperlipidemia during Chemotherapy for Prostate Cancer
Seirei Mikatahara General Hospital Hamamatsu, JAPAN
Disclosure(s):
Masayasu Iwabuchi, MD,PhD: No financial relationships to disclose
Background: Hyperlipidemia may be present in cancer patients despite their debilitated general condition. It has also been reported that several types of cancer cells produce PCSK9. It is reported that PCSK9 regulates LDL receptor degradation, impacting cholesterol levels, which are crucial for cancer cell growth, furthermore PCSK9 can suppress anti-tumor immunity by hindering T-cells from recognizing cancer cells, potentially increasing resistance to immunotherapy. Inclisiran sodium is a double-stranded small interfering RNA (siRNA), which inhibits the transcription of PCSK9. Recent studies indicate that PACT (protein activator of the interferon-induced protein kinase), which is encoded by the PRKRA gene, plays a pro-proliferative role in prostate cancer. While Inclisiran sodium is a specific siRNA approved for lowering cholesterol, the research on PACT points towards siRNA-based targeting of this protein as a potential therapeutic approach to reduce tumor growth in advanced prostate cancer. Abiraterone acetate is a medicine used to treat prostate cancer when the cancer is metastatic. A patient with advanced prostate cancer and hyperlipidemia was treated with Abiraterone acetate and Inclisiran sodium and followed while continuing chemotherapy with abiraterone acetate for prostate cancer.
Case: A man in his 70s visited a urologist due to frequent urination and was diagnosed with cT3bN0M1b prostate cancer, with a PSA level of 901ng/dL. Chemotherapy with Abiraterone acetate was initiated and continued, and denosumab was initiated for the bone metastases but was discontinued due to osteonecrosis of the jaw. While the PSA level improved to 0.061 ng/mL, the LDL-C level was abnormally high at 285 mg/dL. The PCSK9 level was abnormally high at 449 ng/mL (normal range 89.5 ± 31.9). Since statins have been reported to increase PCSK9 levels, 300mg of Inclisiran sodium was administered, which may contribute to anti-tumor effects. Inclisiran sodium reduced PCSK9 level and LDL cholesterol level to 116 mg/dL. In combination with ongoing chemotherapy, PSA levels also decreased to 0.022 ng/mL. Bone metastases were also suppressed, and activities of daily living are well maintained. CLINICAL LESSONS: This is the first case report to observe the effects of concomitant use of Inclisiran sodium for hyperlipidemia that developed during chemotherapy for prostate cancer. While Inclisiran sodium is a specific siRNA approved for lowering cholesterol, the research on PACT points towards siRNA-based targeting of this protein as a potential therapeutic approach to reduce tumor growth in advanced prostate cancer. PCSK9 inhibitors, initially developed to treat hypercholesterolemia, may have significant involvement in the treatment of various cancers and their metastases.
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