Chronological Liquid Biopsy Reveals the Impact of Platinum-Based Chemotherapy on a Prostate Cancer Patient’s CDK12 Mutation: A Case Report

Abstract

CDK12 (Cyclin-Dependent Kinase 12)-mutated prostate cancer patients often respond badly to current therapies. Immunotherapy and platinum-based chemotherapy are recommended based on the molecular features of CDK12 -mutated tumors, but the reported patient outcomes are still unsatisfying. Here we report a prostate cancer patient with CDK12 somatic mutation who received multiple therapy options, including platinum-based chemotherapy and immunotherapy. His sequential circulating tumor DNA (ctDNA) -based liquid biopsy tests showed that his original CDK12 mutation fell undetectable twice. This phenomenon was observed only when he was responding well to platinum-based chemotherapy. His responses to immunotherapy were not satisfying. This case indicates that platinum-based chemotherapy can be a good option for treating patients with CDK12 mutation. More importantly, dynamic ctDNA-based liquid biopsies to monitor patients’ CDK12 mutation status are critical in evaluating patients’ response and tolerance during platinum-based chemotherapy, therefore may lead to a better overall prognosis. In conclusion, CDK12 -mutated prostate cancer patients are likely to benefit from platinum-based chemotherapy, especially with the help of dynamic ctDNA-based liquid biopsies to monitor their CDK12 mutation status.

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis

“… Zhu et al (2022) reported a case of a 55-year-old male with CDK12-mutated PCa diagnosed with the help of circulating tumor DNA. Basnet et al (2017) present a unique case of a male patient aged 65 years with mCRPC, and primarily local failure in the pelvis.…”

“… Zhu et al (2022) primarily administered Cis-Platinum chemotherapy to the CDK12 mutated PCa patient. Essentially, a literature-supported PD-1 inhibitor was administered in the last year of survival ( Zhu et al, 2022 ).…”

“… Zhu et al (2022) primarily administered Cis-Platinum chemotherapy to the CDK12 mutated PCa patient. Essentially, a literature-supported PD-1 inhibitor was administered in the last year of survival ( Zhu et al, 2022 ). Basnet and colleagues (2017) used Nivolumab, a PD-1 blocker, as a fifth-line agent once the patient became refractory to chemotherapies and Enzalutamide.…”

“…Sena et al (2021) presented a 60-year-old male patient diagnosed with brain metastases due to PCa who had castration-resistant, mismatch repairdeficient disease with MLH1 loss. Zhu et al (2022) reported a case of a 55-year-old male with CDK12-mutated PCa diagnosed with the help of circulating tumor DNA. Basnet et al (2017) present a unique case of a male patient aged 65 years with mCRPC, and primarily local failure in the pelvis.…”

Liquid Biopsy: A New Emerging Technique

“…Despite good initial response to Androgen Deprivation Therapy (ADT), tumors eventually progress to metastatic castration resistant PCa (mCRPC). Liquid biopsy assays, analyzing circulating free tumor DNA (ctDNA) or circulating tumor cells (CTCs) in plasma or other body fluids have proven as a useful source for biomarkers and have already entered the clinics [1] as to this date, mCRPC remains an incurable disease [1] CDK12(Cyclin-Dependent Kinase)-mutated prostate cancer patients are likely to benefit from platinum-based chemotherapy, especially with the help of dynamic ctDNA-based liquid biopsies to monitor their CDK12 mutation status [2]. Liquid biopsy is a powerful tool for isolating genetic material, proteins, and whole tumor cells from the blood.…”