{"title":"The development of ATR inhibitors.","authors":"Timothy A Yap","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":51585,"journal":{"name":"Clinical Advances in Hematology & Oncology","volume":"23 3","pages":"185-187"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prostate cancer is a highly heritable cancer, with contributions from rare pathogenic variants in prostate cancer predisposition genes (eg, HOXB13, BRCA2) and from common genetic variants throughout the genome. Only HOXB13 has been identified as a prostate cancer risk gene through linkage disequilibrium studies. Cancer predisposition genes in DNA damage repair pathways have been found to contribute to prostate cancer risk-particularly high-risk or metastatic prostate cancers-in family-based, clinic-based, and population-based studies. Polygenic and genomic risk scores based on common genetic variants identified in genome-wide association studies may have greater power to determine cancer risk than scores based on rare pathogenic variants, but the utility of these scores has yet to be rigorously studied prospectively. Individuals with high-risk or metastatic prostate cancers should be offered germline genetic testing to inform familial risk and screening practices, and to identify biomarker-based treatment options such as platinum-based chemotherapy or poly(ADP-ribose) polymerase inhibitors. Much work is needed to increase the use of germline genetic testing in individuals with prostate cancer, to improve equitable access to testing across all ethnic and racial groups, and to study the genomes of non-European ancestral populations in greater numbers to identify additional ancestry-specific risk variants.
{"title":"Genetics of prostate cancer.","authors":"Jeffrey W Shevach, Kathleen A Cooney","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate cancer is a highly heritable cancer, with contributions from rare pathogenic variants in prostate cancer predisposition genes (eg, HOXB13, BRCA2) and from common genetic variants throughout the genome. Only HOXB13 has been identified as a prostate cancer risk gene through linkage disequilibrium studies. Cancer predisposition genes in DNA damage repair pathways have been found to contribute to prostate cancer risk-particularly high-risk or metastatic prostate cancers-in family-based, clinic-based, and population-based studies. Polygenic and genomic risk scores based on common genetic variants identified in genome-wide association studies may have greater power to determine cancer risk than scores based on rare pathogenic variants, but the utility of these scores has yet to be rigorously studied prospectively. Individuals with high-risk or metastatic prostate cancers should be offered germline genetic testing to inform familial risk and screening practices, and to identify biomarker-based treatment options such as platinum-based chemotherapy or poly(ADP-ribose) polymerase inhibitors. Much work is needed to increase the use of germline genetic testing in individuals with prostate cancer, to improve equitable access to testing across all ethnic and racial groups, and to study the genomes of non-European ancestral populations in greater numbers to identify additional ancestry-specific risk variants.</p>","PeriodicalId":51585,"journal":{"name":"Clinical Advances in Hematology & Oncology","volume":"23 3","pages":"144-152"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Treatment deintensification in locally advanced rectal cancer: when less is more.","authors":"Andrea Cercek","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":51585,"journal":{"name":"Clinical Advances in Hematology & Oncology","volume":"23 3","pages":"182-184"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ethics in medicine: avoiding conflicts of interest in prescribing.","authors":"Gail Van Norman","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":51585,"journal":{"name":"Clinical Advances in Hematology & Oncology","volume":"23 2","pages":"93-95"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The use of fixed-dose regimens in chronic lymphocytic leukemia.","authors":"Arnon Kater","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":51585,"journal":{"name":"Clinical Advances in Hematology & Oncology","volume":"23 2","pages":"84-86"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors (PARPis) were first granted US Food and Drug Administration (FDA) approval for ovarian cancer. Trials have focused on high-grade serous histology, in which BRCA mutations and homologous recombination deficiency (HRD) are most common. The initial clinical trials of PARPis were performed in patients with heavily pretreated recurrent BRCA-mutated (BRCAm) ovarian cancer. Since then, concerns over possible reductions in overall survival with long-term PARPi treatment in recurrent disease have led to the withdrawal of most FDA approvals in this setting, and the use of PARPis has moved to the maintenance setting in newly diagnosed advanced ovarian cancer, in which trials have demonstrated significant progression-free survival benefits and trends for overall survival benefit with certain PARPis in patients who have BRCA mutations. Additionally, the risks of secondary acute myeloid leukemia and myelodysplastic syndrome are lower in the newly diagnosed setting than in the recurrent setting, potentially because of a predefined duration of PARPi treatment and/or less prior exposure to chemotherapy. Currently, several PARPis are FDA-approved in ovarian cancer: (1) olaparib (BRCAm), niraparib (BRCAm and BRCA wild-type [BRCAwt]), and olaparib/bevacizumab (BRCAm and BRCAwt/HRD) as maintenance therapy after platinum in newly diagnosed advanced disease; and (2) olaparib, niraparib, and rucaparib for recurrent BRCAm platinum-sensitive disease. This review discusses PARPi data in the newly diagnosed and recurrent settings, how current FDA approvals have evolved, and PARPi combination data.
{"title":"Update on PARP inhibitors for the treatment of ovarian cancer.","authors":"Joyce Liu, Ursula A Matulonis","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors (PARPis) were first granted US Food and Drug Administration (FDA) approval for ovarian cancer. Trials have focused on high-grade serous histology, in which BRCA mutations and homologous recombination deficiency (HRD) are most common. The initial clinical trials of PARPis were performed in patients with heavily pretreated recurrent BRCA-mutated (BRCAm) ovarian cancer. Since then, concerns over possible reductions in overall survival with long-term PARPi treatment in recurrent disease have led to the withdrawal of most FDA approvals in this setting, and the use of PARPis has moved to the maintenance setting in newly diagnosed advanced ovarian cancer, in which trials have demonstrated significant progression-free survival benefits and trends for overall survival benefit with certain PARPis in patients who have BRCA mutations. Additionally, the risks of secondary acute myeloid leukemia and myelodysplastic syndrome are lower in the newly diagnosed setting than in the recurrent setting, potentially because of a predefined duration of PARPi treatment and/or less prior exposure to chemotherapy. Currently, several PARPis are FDA-approved in ovarian cancer: (1) olaparib (BRCAm), niraparib (BRCAm and BRCA wild-type [BRCAwt]), and olaparib/bevacizumab (BRCAm and BRCAwt/HRD) as maintenance therapy after platinum in newly diagnosed advanced disease; and (2) olaparib, niraparib, and rucaparib for recurrent BRCAm platinum-sensitive disease. This review discusses PARPi data in the newly diagnosed and recurrent settings, how current FDA approvals have evolved, and PARPi combination data.</p>","PeriodicalId":51585,"journal":{"name":"Clinical Advances in Hematology & Oncology","volume":"23 2","pages":"100-110"},"PeriodicalIF":1.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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