Poor response to selpercatinib plus crizotinib in a rearranged during transfection fusion-positive patient with acquired selpercatinib-resistant MNNG HOS transforming amplification: a case report.

Selpercatinib has been approved by most major regulatory bodies in 2020 and become the standard therapy for rearranged during transfection ( RET )-rearranged nonsmall-cell lung cancer (NSCLC). Knowledge is limited regarding mechanisms of resistance to selpercatinib and effective treatment. One study identified MNNG HOS transforming ( MET ) amplification as intrinsic or secondary resistance mechanism from four patients, and three of them showed ~40% tumor reduction when treated with selpercatinib plus crizotinib. We report a 30-year-old female nonsmoker diagnosed in 2019 with stage IV lung adenocarcinoma harboring KIF5B-RET and a novel FOXD1-RET fusion. Frontline therapy consisted of bevacizumab combined with pemetrexed and carboplatin and achieved a progression-free survival (PFS) of 14 months with best response of stable disease. The patient then enrolled in the LIBRETTO-321 trial (NCT03157129) and started selpercatinib, which elicited a PFS of 9 months with best response of partial response. MNNG HOS transforming ( MET ) amplification was subsequently detected upon progression on selpercatinib, and the patient was placed on third-line treatment with selpercatinib plus crizotinib. However, her health deteriorated rapidly and died of cancer 4 months later. We provided additional evidence supporting MET amplification as an acquired mechanism of resistance to selective RET inhibition. In addition, the apparent lack of response to selpercatinib plus crizotinib in this case highlights the need for future cohort studies for examining the value of combining RET and MET inhibitors in treating RET -rearranged, MET -amplified NSCLC.

[Association between the polymorphism of CYP17 gene and risk of prostate cancer in chinese vigurs men].

OBJECTIVE: To investigate the association between the polymorphism of CYP17 gene and risk of prostate cancer in Chinese Vigurs men. METHODS: A case-control study including 31 patients with prostate cancer and 104 aged-matched controls was conducted. The polymorphism was investigated by PCR using DNA from peripheral blood lymphocytes. The transition (T-->C) in the risk allele (A2) produced a new recognition site for the restriction enzyme MSPAI I. Three genotypes of CYP17 gene (A1/A1, A1/A2, A2/A2) were determined and confirmed by sequencing. RESULTS: Compared with male A1/A1 genotype, the odds ratios were 1.49 and 2.87 for the A1/A2 and A2/A2 genotypes (P =0.321, 0. 052, respectively). Comparison among 3 subgroups (division by genetypes) of prostate cancer patients, the PSA levels were not significantly different. But in the controls, PSA levels in A1/A2 group were higher but not significant than those in A1/A1 group (P = 0.062). Then, PSA levels in A2/A2 group were significantly higher than those A1/ A1 group (P = 0.018). CONCLUSION: More frequency of A2/A2 genotype in prostate cancer than in the control may be associated with the morbidity of prostate cancer in Vigurs male population. Meanwhile, the significant high PSA levels in A2/A2 group also support the view.

Association between the polymorphism of CYP17 gene and risk of prostate cancer in chinese vigurs men / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the association between the polymorphism of CYP17 gene and risk of prostate cancer in Chinese Vigurs men.</p><p><b>METHODS</b>A case-control study including 31 patients with prostate cancer and 104 aged-matched controls was conducted. The polymorphism was investigated by PCR using DNA from peripheral blood lymphocytes. The transition (T-->C) in the risk allele (A2) produced a new recognition site for the restriction enzyme MSPAI I. Three genotypes of CYP17 gene (A1/A1, A1/A2, A2/A2) were determined and confirmed by sequencing.</p><p><b>RESULTS</b>Compared with male A1/A1 genotype, the odds ratios were 1.49 and 2.87 for the A1/A2 and A2/A2 genotypes (P =0.321, 0. 052, respectively). Comparison among 3 subgroups (division by genetypes) of prostate cancer patients, the PSA levels were not significantly different. But in the controls, PSA levels in A1/A2 group were higher but not significant than those in A1/A1 group (P = 0.062). Then, PSA levels in A2/A2 group were significantly higher than those A1/ A1 group (P = 0.018).</p><p><b>CONCLUSION</b>More frequency of A2/A2 genotype in prostate cancer than in the control may be associated with the morbidity of prostate cancer in Vigurs male population. Meanwhile, the significant high PSA levels in A2/A2 group also support the view.</p>