Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has been a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer. Evidence-based further line therapy options in the metastatic setting include T-DM1 and in later lines Lapatinib. For triple negative disease the angiogenesis inhibitor Bevacizumab is approved, which increases progression free survival. Immune checkpoint inhibitors, PARP-inhibitors or anti-androgens represent promising strategies, all of which are currently being evaluated in clinical trials. The development of predictive biomarkers to guide targeted therapies is still the subject of research.
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PMID:[Current Status of Targeted Treatment in Breast Cancer]. 2907 12

Within the last years significant improvements have been achieved in early and metastatic breast cancer treatment by innovative targeted therapies and new drug combinations. GnRH-analogues have been confirmed as an important part of endocrine treatment in premenopausal patients. Endocrine based strategies including CDK-4/6-Inhibitors substantially improve progression-free survival in metastatic patients. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has achieved a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer. For triple-negative disease chemotherapy is still the mainstay of treatment. Immune checkpoint inhibitors represent promising strategies in this cohort, which are currently being evaluated in clinical trials. PARP inhibitors will be available as innovative treatment concept in BRCA1/2 mutation carriers.
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PMID:[Systemic Treatment of Early and Metastatic Breast Cancer]. 3050 53

Significant advancements have been made in recent years in advanced breast cancer and nearly all of them have been in the field of targeted therapy. Pertuzumab and trastuzumab-emtansine (T-DM1) have been able to be introduced in HER2-positive breast cancer. Now other anti-HER2 therapies are being developed (e.g. margetuximab, DS-8201a, pyrotinib) which can overcome other resistance mechanisms in the HER2 signalling pathway. In the field of hormone-receptor-positive breast cancer, an mTOR inhibitor and CDK4/6 inhibitors were introduced in the past. Now the introduction of the first PI3K inhibitor is forthcoming and this inhibitor will involve genetic testing of the tumour for a mutation in the PIK3CA gene. There are also significant advancements in triple-negative breast cancer: By combining chemotherapy and immunotherapy, an advantage for overall survival was able to be demonstrated in a subgroup (immune cells PD-L1-positive). The PARP inhibitor therapy for HER2-negative patients with a germ line mutation in BRCA1 or BRCA2 was also associated with an improved overall survival in a subgroup. These promising new study results are summarised in this review.
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PMID:Update Breast Cancer 2019 Part 5 - Diagnostic and Therapeutic Challenges of New, Personalised Therapies in Patients with Advanced Breast Cancer. 3165 19