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Clinical Use of PARP Inhibitors in BRCA Mutant and Non-BRCA Mutant Breast Cancer. PARP抑制剂在BRCA突变型和非BRCA突变型乳腺癌中的临床应用
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-30065-3_6
Filipa Lynce, Mark Robson
{"title":"Clinical Use of PARP Inhibitors in BRCA Mutant and Non-BRCA Mutant Breast Cancer.","authors":"Filipa Lynce, Mark Robson","doi":"10.1007/978-3-031-30065-3_6","DOIUrl":"10.1007/978-3-031-30065-3_6","url":null,"abstract":"<p><p>The use of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of patients with germline BRCA mutations (gBRCAm) and breast cancer, both in the early and advanced settings, is a success of genomically-directed treatment. These agents have been shown to be associated with longer progression-free survival when compared to standard chemotherapy, with an acceptable toxicity profile. A recent randomized trial demonstrated improved survival with the use of olaparib for 2 years compared to placebo in patients with early-stage high risk gBRCAm associated breast cancer. Ongoing research efforts are focused on identifying patients beyond those with BRCA1/2 or PALB2 mutations who may benefit from PARP inhibitors, exploring the overlapping mechanisms of resistance between platinum and PARP inhibitors and developing agents with less toxicity that will allow combinational strategies.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"186 ","pages":"91-102"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396425","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}
引用次数: 0
Mechanisms of PARP Inhibitor Resistance. PARP抑制剂耐药机制。
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-30065-3_3
Mark J O'Connor, Josep V Forment
{"title":"Mechanisms of PARP Inhibitor Resistance.","authors":"Mark J O'Connor, Josep V Forment","doi":"10.1007/978-3-031-30065-3_3","DOIUrl":"10.1007/978-3-031-30065-3_3","url":null,"abstract":"<p><p>Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) represent the first medicines based on the targeting of the DNA damage response (DDR). PARPi have become standard of care for first-line maintenance treatment in ovarian cancer and have also been approved in other cancer indications including breast, pancreatic and prostate. Despite their efficacy, resistance to PARPi has been reported clinically and represents a growing patient population with unmet clinical need. Here, we describe the various mechanisms of PARPi resistance that have been identified in pre-clinical models and in the clinic.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"186 ","pages":"25-42"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396512","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}
引用次数: 0
Rational Combinations of PARP Inhibitors with HRD-Inducing Molecularly Targeted Agents. PARP抑制剂与hrd诱导分子靶向药物的合理联合。
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-30065-3_10
Elizabeth K Lee, Joyce F Liu
{"title":"Rational Combinations of PARP Inhibitors with HRD-Inducing Molecularly Targeted Agents.","authors":"Elizabeth K Lee, Joyce F Liu","doi":"10.1007/978-3-031-30065-3_10","DOIUrl":"10.1007/978-3-031-30065-3_10","url":null,"abstract":"<p><p>Cancers with wild-type BRCA, homologous recombination proficiency, or de novo or acquired resistance to PARP inhibition represent a growing population of patients who may benefit from combinatorial PARP inhibitor strategies. We review targeted inhibitors of angiogenesis, epigenetic regulators, and PI3K, MAPK, and other cellular signaling pathways as inducers of homologous recombination deficiency, providing support for the use of PARP inhibitors in contexts not previously considered susceptible to PARP inhibition.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"186 ","pages":"171-188"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396514","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}
引用次数: 0
Strategies for the Management of Patients with Pancreatic Cancer with PARP Inhibitors. 胰腺癌患者PARP抑制剂的治疗策略
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-30065-3_8
Talia Golan, Maria Raitses-Gurevich, Tamar Beller, James Carroll, Jonathan R Brody
{"title":"Strategies for the Management of Patients with Pancreatic Cancer with PARP Inhibitors.","authors":"Talia Golan, Maria Raitses-Gurevich, Tamar Beller, James Carroll, Jonathan R Brody","doi":"10.1007/978-3-031-30065-3_8","DOIUrl":"10.1007/978-3-031-30065-3_8","url":null,"abstract":"<p><p>A subset of patients with pancreatic adenocarcinomas (PDAC) harbor mutations that are exploitable in the context of DNA-damage response and repair (DDR) inhibitory strategies. Between 8-18% of PDACs harbor specific mutations in the DDR pathway such as BRCA1/2 mutations, and a higher prevalence exists in high-risk populations (e.g., Ashkenazi Jews). Herein, we will review the current trials and data on the treatment of PDAC patients who harbor such mutations and who appear sensitive to platinum and/or poly ADP ribose polymerase inhibitor (PARPi) based therapies due to a concept known as synthetic lethality. Although this current best-in-class precision treatment shows clinical promise, the specter of resistance limits the extent of therapeutic responses. We therefore also evaluate promising pre-clinical and clinical approaches in the pipeline that may either work with existing therapies to break resistance or work separately with combination therapies against this subset of PDACs.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"186 ","pages":"125-142"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396515","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}
引用次数: 0
Combining PARP Inhibition and Immunotherapy in BRCA-Associated Cancers. 联合PARP抑制和免疫治疗brca相关癌症。
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-30065-3_12
Geoffrey I Shapiro, Suzanne M Barry
{"title":"Combining PARP Inhibition and Immunotherapy in BRCA-Associated Cancers.","authors":"Geoffrey I Shapiro, Suzanne M Barry","doi":"10.1007/978-3-031-30065-3_12","DOIUrl":"10.1007/978-3-031-30065-3_12","url":null,"abstract":"<p><p>Poly (ADP-ribose) polymerase (PARP) inhibitors have significantly improved treatment outcomes of homologous recombination (HR) repair-deficient cancers. While the activity of these agents is largely linked to multiple mechanisms underlying the synthetic lethality of PARP inhibition and HR deficiency, emerging data suggest that their efficacy is also tied to their effects on the immune microenvironment and dependent upon cytotoxic T-cell activation. Effects observed in preclinical models are currently being validated in on-treatment biopsy samples procured from patients enrolled in clinical trials. Although this work has stimulated the development of combinations of PARP inhibitors with immunomodulatory agents, results to date have not demonstrated the superiority of combined PARP inhibition and immune checkpoint blockade compared with PARP inhibition alone. These results have stimulated a more comprehensive assessment of the immunosuppressive components of the tumor microenvironment that must be addressed so that the efficacy of PARP inhibitor agents can be maximized.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"186 ","pages":"207-221"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396427","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}
引用次数: 0
Advance Care Planning Conversations: Laying the Foundation for Goal-Concordant Care at End of Life. 预先护理计划对话：为生命末期目标一致的护理奠定基础。
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-29923-0_6
Abigail Nathanson, Shirley Otis-Green
{"title":"Advance Care Planning Conversations: Laying the Foundation for Goal-Concordant Care at End of Life.","authors":"Abigail Nathanson,&nbsp;Shirley Otis-Green","doi":"10.1007/978-3-031-29923-0_6","DOIUrl":"10.1007/978-3-031-29923-0_6","url":null,"abstract":"<p><p>The delivery of culturally congruent, person-centered, family-focused quality care requires an exploration of the values, beliefs, and preferences of those we serve [13]. Nuanced advance care planning conversations lay the foundation for shared decision making and promotes the delivery of goal-concordant care. This chapter will provide clinicians with guidance and resources to aid this process with a focus on contextualized communication with those with serious illness.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"187 ","pages":"73-84"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232535","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}
引用次数: 0
Church of Jesus Christ of Latter-Day Saints (also Referred to as the Mormon Church). 耶稣基督后期圣徒教会（也称为摩门教）。
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-29923-0_14
Vicki Pond
{"title":"Church of Jesus Christ of Latter-Day Saints (also Referred to as the Mormon Church).","authors":"Vicki Pond","doi":"10.1007/978-3-031-29923-0_14","DOIUrl":"10.1007/978-3-031-29923-0_14","url":null,"abstract":"<p><p>Members of The Church of Jesus Christ of Latter-day Saints accept modern medical science and believe in receiving medical treatment along with seeking divine guidance and inspiration. At the same time, situations of life and death can throw people into stressful places they have never been before, bringing challenges even to people of deep faith. Medical professionals can better support Latter-day Saints if they understand how their beliefs answer questions about life and death, including, \"Where did I come from? Why am I here on earth? Where am I going after death?\" This chapter examines the origin, beliefs, and practices of the Church to give medical professionals a foundational understanding of what is important to members at the end of life. It includes sections on beliefs and practices, including those relevant to medical treatment, end-of-life decisions, death and burial.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"187 ","pages":"203-218"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232540","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}
引用次数: 0
Cultural Competency Models at the End of Life. 生命终结时的文化能力模型。
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-29923-0_2
Noah Pujanes-Mantor, Sorin Buga
{"title":"Cultural Competency Models at the End of Life.","authors":"Noah Pujanes-Mantor,&nbsp;Sorin Buga","doi":"10.1007/978-3-031-29923-0_2","DOIUrl":"10.1007/978-3-031-29923-0_2","url":null,"abstract":"<p><p>This chapter examines the need and importance of cultural competency in providing End of Life care. The United States is diverse in culture. As we evolve into a multiethnic society, our healthcare providers must be able to manage this shift in establishing and providing care that is culturally appropriate and effective. Americans have the rights to provide autonomy and independent decision-making related to their healthcare; however, these core values may not align with ethnic and culturally diverse groups in the United States. Conflicts often lead to health disparities and resulting in care that is fragmented and inadequate. The difference in values result in improper management and miscommunication with patients and families that significantly affect care, especially during end-of-life.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"187 ","pages":"17-23"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232541","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}
引用次数: 0
End-of-Life Doulas. 生命的终结杜拉斯。
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-29923-0_21
Debbie Salgia, Sari Williams
{"title":"End-of-Life Doulas.","authors":"Debbie Salgia,&nbsp;Sari Williams","doi":"10.1007/978-3-031-29923-0_21","DOIUrl":"10.1007/978-3-031-29923-0_21","url":null,"abstract":"<p><p>Doula is a Greek word meaning \"woman caregiver\", and an \"experienced woman who helps other women\" [4].</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"187 ","pages":"305-311"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232545","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}
引用次数: 0
RNA Modifications in Cancer Metabolism and Tumor Microenvironment. 癌症代谢和肿瘤微环境中的 RNA 修饰
Cancer treatment and research Pub Date : 2023-01-01 DOI: 10.1007/978-3-031-45654-1_1
Ying Qing, Dong Wu, Xiaolan Deng, Jianjun Chen, Rui Su
{"title":"RNA Modifications in Cancer Metabolism and Tumor Microenvironment.","authors":"Ying Qing, Dong Wu, Xiaolan Deng, Jianjun Chen, Rui Su","doi":"10.1007/978-3-031-45654-1_1","DOIUrl":"10.1007/978-3-031-45654-1_1","url":null,"abstract":"<p><p>RNA modifications have recently been recognized as essential posttranscriptional regulators of gene expression in eukaryotes. Investigations over the past decade have revealed that RNA chemical modifications have profound effects on tumor initiation, progression, refractory, and recurrence. Tumor cells are notorious for their robust plasticity in response to the stressful microenvironment and undergo metabolic adaptations to sustain rapid cell proliferation, which is termed as metabolic reprogramming. Meanwhile, cancer-associated metabolic reprogramming leads to substantial alterations of intracellular and extracellular metabolites, which further reshapes the tumor microenvironment (TME). Moreover, cancer cells compete with tumor-infiltrating immune cells for the limited nutrients to maintain their proliferation and function in the TME. In this chapter, we review recent interesting findings on the engagement of epitranscriptomic pathways, especially the ones associated with N<sup>6</sup>-methyladenosine (m<sup>6</sup>A), in the regulation of cancer metabolism and the surrounding microenvironment. We also discuss the promising therapeutic approaches targeting RNA modifications for anti-tumor therapy.</p>","PeriodicalId":9486,"journal":{"name":"Cancer treatment and research","volume":"190 ","pages":"3-24"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797752","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}
引用次数: 0
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