.Antiestrogens in combination with immune checkpoint inhibitors in breast cancer immunotherapy

Publication date: Available online 19 June 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Diana C. Márquez-Garbán, Gang Deng, Begonya Comin-Anduix, Alejandro J. Garcia, Yanpeng Xing, Hsiao-Wang Chen, Gardenia Cheung-Lau, Nalo Hamilton, Michael E. Jung, Richard J. PietrasAbstractBreast cancers (BC) with expression of estrogen receptor-alpha (ERα) occur in more than 70% of newly-diagnosed patients in the U.S. Endocrine therapy with antiestrogens or aromatase inhibitors is an important intervention for BCs that express ERα, and it remains one of the most effective targeted treatment strategies. However, a substantial proportion of patients with localized disease, and essentially all patients with metastatic BC, become resistant to current endocrine therapies. ERα is present in most resistant BCs, and in many of these its activity continues to regulate BC growth. Fulvestrant represents one class of ERα antagonists termed selective ER downregulators (SERDs). Treatment with fulvestrant causes ERα down-regulation, an event that helps overcome several resistance mechanisms. Unfortunately, full antitumor efficacy of fulvestrant is limited by its poor bioavailability in clinic. We have designed and tested a new generation of steroid-like SERDs. Using ERα-positive BC cells in vitro, we find that these compounds suppress ERα protein levels with efficacy similar to fulvestrant. Moreover, these new SER...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research

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Publication date: October 2019Source: The Journal of Steroid Biochemistry and Molecular Biology, Volume 193Author(s): Diana C. Márquez-Garbán, Gang Deng, Begonya Comin-Anduix, Alejandro J. Garcia, Yanpeng Xing, Hsiao-Wang Chen, Gardenia Cheung-Lau, Nalo Hamilton, Michael E. Jung, Richard J. PietrasAbstractBreast cancers (BCs) with expression of estrogen receptor-alpha (ERα) occur in more than 70% of newly-diagnosed patients in the U.S. Endocrine therapy with antiestrogens or aromatase inhibitors is an important intervention for BCs that express ERα, and it remains one of the most effective targete...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research
Abstract Managing endocrine resistance and resistance to endocrine therapy for ER+ HER2- breast cancer with the CDK 4/6 inhibitors in the metastatic setting. New antibodies drug conjugates for HER2+ and TNBC. Targeting DNA damage and synthetic lethality strategies with PARP inhibitors for breast cancer patients harboring BRCA mutation. Immunotherapies in 1st line metastatic setting of TNBC. PMID: 31151842 [PubMed - as supplied by publisher]
Source: Presse Medicale - Category: General Medicine Authors: Tags: Presse Med Source Type: research
Opinion statementOral inhibitors of CDK4/6 have been shown to increase response rates and prolong disease control when combined with endocrine therapy in hormone-responsive (HR+) HER2-negative advanced breast cancer. Palbociclib, ribociclib and abemaciclib are all approved in combination with non-steroidal aromatase inhibitors in first-line therapy for post-menopausal women, with a 40 –45% improvement in progression-free survival seen with the addition of any of these CDK4/6 inhibitors. Additional approved indications, including first- and second-line combination therapy for pre-menopausal women, combination with ful...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, our WGCNA analysis identified candidate prognostic biomarkers for further basic and clinical researches. Introduction Breast cancer is a frequently diagnosed malignancy and the leading cause of cancer death among females around the world, accounting for 24% of cancer diagnoses and 15% of cancer deaths in females. According to Global Cancer Statistics 2018, there will be nearly 2.1 million new cases diagnosed globally, with ~62 thousand deaths. The incident rates of breast cancer increased in most developing countries during last decades, resulting from a combination of social and economic factors, incl...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
(CNN) — Surgery is tied to improved chances of survival among stage 4 breast cancer patients, a new study suggests, but who has access to surgery and who doesn’t can vary drastically, based on factors including income level and where treatment is administered. Surgery to remove tumors was associated with a 44% increased chance of survival within an average followup period of 21 months, according to the abstract, to be presented at the American Association for Cancer Research’s annual meeting in Atlanta this week. “If breast surgery is to be considered by patients and providers when deciding treatmen...
Source: WBZ-TV - Breaking News, Weather and Sports for Boston, Worcester and New Hampshire - Category: Consumer Health News Authors: Tags: Health News Breast Cancer CNN Source Type: news
Publication date: Available online 19 June 2018Source: Pharmacology &TherapeuticsAuthor(s): Filipa Lynce, Ayesha N. Shajahan-Haq, Sandra M. SwainAbstractDysregulation of the cyclin dependent kinase pathway in luminal breast cancer creates a new therapeutic opportunity for estrogen receptor positive breast cancer. Initial pan-CDK inhibitors were associated with extensive toxicities but in recent years, the development of potent specific CDK inhibitors with favorable tolerability has driven renewed interests in this class of targeted therapies. Palbociclib, ribociclib and abemaciclib are specific CDK4/6 inhibitors that h...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research
Authors: Giordano SH, Elias AD, Gradishar WJ Abstract The emergence of CDK4/6 inhibitors has changed the treatment algorithm for advanced/metastatic estrogen receptor-positive breast cancer. In pivotal trials of palbociclib, ribociclib, and abemaciclib, doubling in progression-free survival has been seen. All 3 agents in this class are now included in the NCCN Guidelines for Breast Cancer, and clinicians should be incorporating these agents into their treatment algorithms. The other important issue in this breast cancer setting is extended duration of endocrine therapy. Most of the benefit is modest and toxicity is...
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
(Bentham Science Publishers) The Authors review immunotherapy attempts to treat metastatic breast cancer. They include a) the addition of cytokines to endocrine therapy, b) monoclonal antibodies associated to chemotherapy and c) vaccination.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
Authors: Suh DH, Kim M, Lee KH, Eom KY, Kjeldsen MK, Mirza MR, Kim JW Abstract In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and ...
Source: Journal of Gynecologic Oncology - Category: OBGYN Tags: J Gynecol Oncol Source Type: research
Authors: Wang J, Zhou P Abstract Despite significant advances in surgery, chemotherapy, radiotherapy, endocrine therapy, and molecular-targeted therapy, breast cancer remains the leading cause of death from malignant tumors among women. Immunotherapy has recently become a critical component of breast cancer treatment with encouraging activity and mild safety profiles. CAR-T therapy using genetically modifying T cells with chimeric antigen receptors (CAR) is the most commonly used approach to generate tumor-specific T cells. It has shown good curative effect for a variety of malignant diseases, especially for hemato...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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