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Isoprenylcysteine Carboxylmethyltransferase-Based Therapy regarding Hutchinson-Gilford Progeria Malady.
Urgent talar relocation restores ankle and hindfoot anatomy and reduces pressure on surrounding soft tissues to optimize outcome. A closed reduction maneuver should be attempted initially, followed by urgent open reduction when the talus is not accurately reduced through closed means.
Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers and has an incidence as high as 50% of brain metastases once patients develop advanced disease. The lack of targeted and effective therapies, characteristic of this subtype of breast cancer, is especially evident once central nervous system (CNS) metastases occur. Compared with other subtypes of breast cancer, TNBC patients have the shorter interval from diagnosis to development of brain metastases and the shorter overall survival once they occur, a median of 4 to 6 months. Preclinical studies of TNBC and CNS microenvironment are actively ongoing, clarifying mechanisms and orienting more effective approaches to therapy. While the first drugs have been specifically approved for use in metastatic TNBC, data on their CNS effect are still awaited.
Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers and has an incidence as high as 50% of brain metastases once patients develop advanced disease. The lack of targeted and effective therapies, characteristic of this subtype of breast cancer, is especially evident once central nervous system (CNS) metastases occur. Compared with other subtypes of breast cancer, TNBC patients have the shorter interval from diagnosis to development of brain metastases and the shorter overall survival once they occur, a median of 4 to 6 months. Preclinical studies of TNBC and CNS microenvironment are actively ongoing, clarifying mechanisms and orienting more effective approaches to therapy. While the first drugs have been specifically approved for use in metastatic TNBC, data on their CNS effect are still awaited.
Poly(ADP-ribose) polymerase (PARP) is involved in single-strand DNA break base excision repair. PARP inhibition causes synthetic lethality in breast cancers associated with germline BRCA1 and BRCA2 mutations and is routinely used in clinical practice for metastatic breast cancer. Breast cancers with homologous recombination deficiency or BRCAness, most commonly triple-negative breast cancers, may also benefit. Currently, PARP inhibitor use for triple-negative breast cancer with wild-type BRCA does not have definitive efficacy; however, this is an area of active research. Further clinical and translational data may identify additional patient populations that will benefit from PARP inhibitor therapy.
Poly(ADP-ribose) polymerase (PARP) is involved in single-strand DNA break base excision repair. PARP inhibition causes synthetic lethality in breast cancers associated with germline BRCA1 and BRCA2 mutations and is routinely used in clinical practice for metastatic breast cancer. Breast cancers with homologous recombination deficiency or BRCAness, most commonly triple-negative breast cancers, may also benefit. Currently, PARP inhibitor use for triple-negative breast cancer with wild-type BRCA does not have definitive efficacy; however, this is an area of active research. Further clinical and translational data may identify additional patient populations that will benefit from PARP inhibitor therapy.
Triple-negative breast cancer (TNBC) is an aggressive subtype of mammary carcinoma. A subset of TNBC is immune activated, suggesting that immunotherapy may be a viable treatment strategy. Phase III clinical trials have shown that atezolizumab or pembrolizumab is well-tolerated in combination with chemotherapy, with progression-free survival benefit in metastatic programmed death ligand-1 (PD-L1)-positive TNBC patients treated first line. Based on IMpassion130, the combination of atezolizumab and nab-paclitaxel is now considered a standard of care for the treatment of PD-L1-positive advanced TNBC. In early TNBC, pembrolizumab and atezolizumab have been tested in combination with standard neoadjuvant chemotherapy, resulting in a higher complete pathologic response rate than standard neoadjuvant chemotherapy alone, regardless of disease PD-L1 status. These findings establish proof of principle for immunotherapy in both early and advanced TNBC. DNA Damage inhibitor High priorities for the field include developing more active immunoof principle for immunotherapy in both early and advanced TNBC. High priorities for the field include developing more active immunotherapy combination regimens and more refined biomarkers that optimally identify patients most likely to benefit from immunotherapy.
Triple-negative breast cancer is increasingly recognized as a heterogeneous entity that can be categorized according to histologic, molecular, and clinical subtypes. While chemotherapy remains the backbone of treatment for this disease, there are now several available targeted agents including immunotherapy, poly(adenosine diphosphate-ribose) polymerase inhibitors, and most recently a Food and Drug Administration-approved antibody-drug conjugate sacituzumab govitecan-hziy as a third-line treatment of metastatic triple-negative breast cancer. We review several actionable targets for triple-negative breast cancer and describe promising nonimmunotherapeutic agents including cyclin-dependent kinase inhibitors, androgen receptor inhibitors, mitogen-activated protein kinase inhibitors, phosphoinositide 3-kinase inhibitors, AKT (also known as protein kinase B) inhibitors, and antibody-drug conjugates.
Triple-negative breast cancer is increasingly recognized as a heterogeneous entity that can be categorized according to histologic, molecular, and clinical subtypes. While chemotherapy remains the backbone of treatment for this disease, there are now several available targeted agents including immunotherapy, poly(adenosine diphosphate-ribose) polymerase inhibitors, and most recently a Food and Drug Administration-approved antibody-drug conjugate sacituzumab govitecan-hziy as a third-line treatment of metastatic triple-negative breast cancer. We review several actionable targets for triple-negative breast cancer and describe promising nonimmunotherapeutic agents including cyclin-dependent kinase inhibitors, androgen receptor inhibitors, mitogen-activated protein kinase inhibitors, phosphoinositide 3-kinase inhibitors, AKT (also known as protein kinase B) inhibitors, and antibody-drug conjugates.
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