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)

Triple negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer accounting for 15-20% of cases and is defined by the lack of hormonal receptors viz., estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth receptor 2 (HER2). Treatment of TNBC is more challenging than other subtypes of breast cancer due to the lack of markers for the molecularly targeted therapies (ER, PR, and HER-2/ Neu), the conventional chemotherapeutic agents are still the mainstay of the therapeutic protocols of its patients. Despite, TNBC being more chemo-responsive than other subtypes, unfortunately, the initial good response to the chemotherapy eventually turns into a refractory drug-resistance. Using a monotherapy for the treatment of cancer, especially high-grade tumors like TNBC, is mostly worthless due to the inherent genetic instability of tumor cells to develop intrinsic and acquired resistance. Thus, a cocktail of two or more drugs with different mechanisms of action is more effective and could successfully control the disease. Furthermore, combination therapy reveals more, or at least the same, effectiveness with lower doses of every single agent and decreases the likelihood of chemoresistance. Herein, we shed light on the novel combinatorial approaches targeting PARP, EGFR, PI3K pathway, AR, and wnt signaling, HDAC, MEK pathway for efficient treatment of high-grade tumors like TNBC and decreasing the onset of resistance.
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PMID:Targeting Different Pathways Using Novel Combination Therapy in Triple Negative Breast Cancer. 3241 25

Breast cancer (BC) is one of the most prevalent cancers in women. Triple-negative breast cancer (TNBC) in which the three major receptors i.e. estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), are absent is known to express the most aggressive phenotype and increased metastasis which results in the development of resistance to chemotherapy. It offers various therapeutic advantages in treating BC and TNBC. Nanotechnology offers various unique characteristics such as small size (nanometric), active and passive targeting, and the ability to attach multiple targeting moieties, controlled release, and site-specific targeting. This review focuses on conventional drug therapies, recent treatment strategies, and unique therapeutic approaches available for BC and TNBC. The role of breast cancer stem cells in the recurrence of BC and TNBC has also been highlighted. Several chemotherapeutic agents delivered using nanocarriers such as polymeric nanoparticles/micelles, metallic/inorganic NPs, and lipid-based NPs (Liposome, solid-lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs)), etc. with excellent responses in the treatment of BC/TNBC along with breast cancer stem cells have been discussed in details. Moreover, the application of nanomedicine including CRISPR nanoparticle, exosomes for the treatment of BC/TNBC and other molecular targets available such as poly (ADP-ribose) polymerase (PARP), epidermal growth factor receptor (EGFR), Vascular endothelial growth factor (VEGF), etc. for further exploration have also been discussed.
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PMID:A review of nanotechnology-based approaches for breast cancer and triple-negative breast cancer. 3265 2

Nearly all breast cancer deaths result from metastatic disease. Despite this, the genomic events that drive metastatic recurrence are poorly understood. We performed whole-exome and shallow whole-genome sequencing to identify genes and pathways preferentially mutated or copy-number altered in metastases compared with the paired primary tumors from which they arose. Seven genes were preferentially mutated in metastases - MYLK, PEAK1, SLC2A4RG, EVC2, XIRP2, PALB2, and ESR1 - 5 of which are not significantly mutated in any type of human primary cancer. Four regions were preferentially copy-number altered: loss of STK11 and CDKN2A/B, as well as gain of PTK6 and the membrane-bound progesterone receptor, PAQR8. PAQR8 gain was mutually exclusive with mutations in the nuclear estrogen and progesterone receptors, suggesting a role in treatment resistance. Several pathways were preferentially mutated or altered in metastases, including mTOR, CDK/RB, cAMP/PKA, WNT, HKMT, and focal adhesion. Immunohistochemical analyses revealed that metastases preferentially inactivate pRB, upregulate the mTORC1 and WNT signaling pathways, and exhibit nuclear localization of activated PKA. Our findings identify multiple therapeutic targets in metastatic recurrence that are not significantly mutated in primary cancers, implicate membrane progesterone signaling and nuclear PKA in metastatic recurrence, and provide genomic bases for the efficacy of mTORC1, CDK4/6, and PARP inhibitors in metastatic breast cancer.
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PMID:Genomic landscape of metastatic breast cancer identifies preferentially dysregulated pathways and targets. 3265 79

Triple-negative breast cancer (TNBC), a highly aggressive breast cancer subtype that lacks estrogen receptor, progesterone receptor, and HER2 expression, does not respond to traditional endocrine and anti-HER2-targeted therapies. Current treatment options for patients with TNBC include a combination of surgery, radiotherapy, and/or systemic chemotherapy. FDA-approved therapies that target DNA damage repair mechanisms in TNBC, such as PARP inhibitors, only provide marginal clinical benefit. The immunogenic nature of TNBC has prompted researchers to harness the body's natural immune system to treat this aggressive breast cancer. Clinical precedent has been recently established with the FDA approval of two TNBC immunotherapies, including an antibody-drug conjugate and an anti-programmed death-ligand 1 monoclonal antibody. Chimeric antigen receptor (CAR)-T cell therapy, a type of adoptive cell therapy that combines the antigen specificity of an antibody with the effector functions of a T cell, has emerged as a promising immunotherapeutic strategy to improve the survival rates of patients with TNBC. Unlike the remarkable clinical success of CAR-T cell therapies in hematologic cancers with Kymriah and Yescarta, the development of CAR-T cell therapies for solid tumors has been much slower and is associated with unique challenges, including a hostile tumor microenvironment. The aim of the present review is to discuss novel approaches and inherent challenges pertaining to CAR-T cell therapy for the treatment of TNBC.
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PMID:Emerging CAR-T Cell Therapy for the Treatment of Triple-Negative Breast Cancer. 3308 11


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