Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, we reported that combined ingestion of soy isoflavones and curcumin significantly decreased the serum level of prostate-specific antigen based on a randomized placebo-controlled double-blind clinical study. We investigated whether these polyphenols inhibited the proliferation of prostate cancer cells by activating a DNA damage response. The effects of isoflavones and curcumin on the expression and phosphorylation of ataxia-telangiectasia-mutated kinase (ATM), histone H2AX variant (H2AX) and checkpoint kinase2 (Chk2) were examined in LNCaP cells. The induction of apoptosis in LNCaP cells was evaluated by poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, the effects of a testosterone supplement on modulation of the DNA damage response were examined. Combined treatment of isoflavones and curcumin additively suppressed cellular proliferation and induced phosphorylation of ATM, histone H2AX, Chk2 and p53. Testosterone augmented the activation of the DNA damage response and PARP cleavage induced by curcumin. Our results indicate that activation of the DNA damage response by polyphenols might suppress the malignant transformation of prostate cancer. In addition, testosterone, when combined with curcumin, may have suppressive effects on the progression of prostate cancer.
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PMID:Testosterone augments polyphenol-induced DNA damage response in prostate cancer cell line, LNCaP. 2113 73

Men who inherit pathogenic germline mutations in BRCA2 and BRCA1 are at increased risk of developing aggressive prostate cancer, and those with germline mutations in other DNA repair genes such as ATM, CHEK2, and MSH2/MSH6 may also have increased risks. Although clinically important, there is lack of specific guidance regarding management strategies for men at increased risk owing to germline mutation status or family history of aggressive prostate cancer. We review prostate cancer genetic risk factors and the ongoing IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) screening study. Pending results of IMPACT and unified guidelines, there are areas of uncertainty and need for further study. Ongoing and future research will be critical for optimizing prostate cancer screening approaches for men at the highest risk for aggressive prostate cancer. In the interim, we propose a practical approach to prostate cancer screening for men with a germline mutation in a known/suspected moderate to high-penetrance cancer predisposition gene (eg, BRCA1/2), and/or men with a first- or second-degree relative with metastatic prostate cancer (regardless of genetic testing): baseline prostate-specific antigen and digital rectal exam by experienced providers at age 40 years or 5 years earlier than age of diagnosis of the youngest first- or second-degree relative with metastatic prostate cancer, whichever is earlier. Then, based on age, digital rectal exam, and prostate-specific antigen, we suggest consideration of magnetic resonance imaging, biopsy, and/or continued monitoring.
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PMID:Prostate Cancer Screening in a New Era of Genetics. 2869 82

New classification systems based on molecular features have been introduced to improve precision medicine for prostate cancer (PCa). This review covers the increasing risk of PCa and the differences in response to targeted therapy that are related to specific gene variations. We believe that genomic evaluations will be useful for guiding PCa risk stratification, screening, and treatment. We searched the PubMed and MEDLINE databases for articles related to genomic testing for PCa that were published in 2020 or earlier. There is increasing evidence that germline mutations in DNA repair genes, such as BRCA1/2 or ATM, are closely related to the development and aggressiveness of PCa. Targeted prostate-specific antigen screening based on the presence of germline alterations in DNA repair genes is recommend to achieve an early diagnosis of PCa. In cases of localized PCa, even if it has a favorable risk classification, patients under active surveillance with these gene alterations are likely to develop aggressive PCa. Thus, active treatment may be preferable to active surveillance for these patients. In cases of metastatic castration-resistant PCa, BRCA1/2 and DNA mismatch repair genes may be useful biomarkers for predicting the response to androgen receptor-targeting agents, poly (ADP-ribose) polymerase inhibitors, platinum chemotherapy, prostate-specific membrane antigen-targeted therapy, immunotherapy, and radium-223. Genomic evaluations may allow for risk stratification of patients with PCa based on their molecular features, which may help guide precision medicine for treating PCa.
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PMID:Clinical implications of genomic evaluations for prostate cancer risk stratification, screening, and treatment: a narrative review. 3310 89