scholarly journals Intratumoural Cytochrome P450 Expression in Breast Cancer: Impact on Standard of Care Treatment and New Efforts to Develop Tumour-Selective Therapies

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 290
Author(s):  
Smarakan Sneha ◽  
Simon C. Baker ◽  
Andrew Green ◽  
Sarah Storr ◽  
Radhika Aiyappa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cytochrome P450 ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Therapeutic Index ◽  
Cancer Cell Proliferation ◽  
Selective Treatment ◽  
Standard Of Care Treatment ◽  
Future Work ◽  
Treat Breast Cancer

Despite significant advances in treatment strategies over the past decade, selective treatment of breast cancer with limited side-effects still remains a great challenge. The cytochrome P450 (CYP) family of enzymes contribute to cancer cell proliferation, cell signaling and drug metabolism with implications for treatment outcomes. A clearer understanding of CYP expression is important in the pathogenesis of breast cancer as several isoforms play critical roles in metabolising steroid hormones and xenobiotics that contribute to the genesis of breast cancer. The purpose of this review is to provide an update on how the presence of CYPs impacts on standard of care (SoC) drugs used to treat breast cancer as well as discuss opportunities to exploit CYP expression for therapeutic intervention. Finally, we provide our thoughts on future work in CYP research with the aim of supporting ongoing efforts to develop drugs with improved therapeutic index for patient benefit.

scholarly journals Use of Targeted Liposome-based Chemotherapeutics to Treat Breast Cancer

2015 ◽  
Vol 9s2 ◽  
pp. BCBCR.S29421 ◽  
Author(s):  
David R. Khan ◽  
Maggie N. Webb ◽  
Thomas H. Cadotte ◽  
Madison N. Gavette
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Clinical Success ◽  
Therapeutic Index ◽  
Cytotoxic Agents ◽  
Phospholipid Bilayer ◽  
Smart Drugs ◽  
Future Work ◽  
Treat Breast Cancer

The use of nanocarriers such as liposomes to deliver anticancer drugs to tumors can significantly enhance the therapeutic index of otherwise unencapsulated cytotoxic agents. This is in part because of the fact that the phospholipid bilayer can protect healthy sensitive tissue from the damaging effects of these types of drugs. Furthermore, the ease with which the phospholipid bilayer surface can be modified to allow for polyethylene glycol incorporation resulting in pegylated liposomes allow for increased circulation times in vivo, and thus an overall increase in the concentration of the drug delivered to the tumor site. This explains the clinical success of the liposomal-based drug Doxil, which has proven to be quite efficacious in the treatment of breast cancer. However, significant challenges remain involving poor drug transfer between the liposome and tumor cells with this type of nontargeted drug delivery system. Thus, future work involves the development of “smart” drugs, or targeted drug delivery intended for improved colocalization between the drug and cancerous cells. While it is not possible to entirely discuss such a rapidly growing field of study involving many different types of chemotherapeutics here, in this review, we discuss some of the recent advancements involving the development of targeted liposome-based chemotherapeutics to treat breast cancer.

scholarly journals A lysosome independent role for TFEB in activating DNA repair and inhibiting apoptosis in breast cancer cells

2020 ◽  
Vol 477 (1) ◽  
pp. 137-160 ◽  
Author(s):  
Logan Slade ◽  
Dipsikha Biswas ◽  
Francis Ihionu ◽  
Yassine El Hiani ◽  
Petra C. Kienesberger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Cancer Survival ◽  
Death Receptor ◽  
Standard Of Care ◽  
Antitumor Agent ◽  
Interferon Γ ◽  
Standard Of Care Treatment ◽  
Induced Apoptosis

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy with critical roles in several cancers. Lysosomal autophagy promotes cancer survival through the degradation of toxic molecules and the maintenance of adequate nutrient supply. Doxorubicin (DOX) is the standard of care treatment for triple-negative breast cancer (TNBC); however, chemoresistance at lower doses and toxicity at higher doses limit its usefulness. By targeting pathways of survival, DOX can become an effective antitumor agent. In this study, we examined the role of TFEB in TNBC and its relationship with autophagy and DNA damage induced by DOX. In TNBC cells, TFEB was hypo-phosphorylated and localized to the nucleus upon DOX treatment. TFEB knockdown decreased the viability of TNBC cells while increasing caspase-3 dependent apoptosis. Additionally, inhibition of the TFEB-phosphatase calcineurin sensitized cells to DOX-induced apoptosis in a TFEB dependent fashion. Regulation of apoptosis by TFEB was not a consequence of altered lysosomal function, as TFEB continued to protect against apoptosis in the presence of lysosomal inhibitors. RNA-Seq analysis of MDA-MB-231 cells with TFEB silencing identified a down-regulation in cell cycle and homologous recombination genes while interferon-γ and death receptor signaling genes were up-regulated. In consequence, TFEB knockdown disrupted DNA repair following DOX, as evidenced by persistent γH2A.X detection. Together, these findings describe in TNBC a novel lysosomal independent function for TFEB in responding to DNA damage.

scholarly journals Dynamics of Breast Cancer under Different Rates of Chemoradiotherapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Sara B. Mkango ◽  
Nyimvua Shaban ◽  
Eunice Mureithi ◽  
Twalib Ngoma
Keyword(s):  
Breast Cancer ◽  
Gene Therapy ◽  
Decay Rate ◽  
Hormone Therapy ◽  
Cause Of Death ◽  
Breast Tissue ◽  
Treatment Strategies ◽  
Common Cause ◽  
New Treatment ◽  
Treat Breast Cancer

A type of cancer which originates from the breast tissue is referred to as breast cancer. Globally, it is the most common cause of death in women. Treatments such as radiotherapy, chemotherapy, hormone therapy, immunotherapy, and gene therapy are the main strategies in the fight against breast cancer. The present study aims at investigating the effects of the combined radiotherapy and chemotherapy as a way to treat breast cancer, and different treatment approaches are incorporated into the model. Also, the model is fitted to data on patients with breast cancer in Tanzania. We determine new treatment strategies, and finally, we show that when sufficient amount of chemotherapy and radiotherapy with a low decay rate is used, the drug will be significantly more effective in combating the disease while health cells remain above the threshold.

scholarly journals Emerging treatment strategies for breast cancer brain metastasis: from translational therapeutics to real-world experience

2020 ◽  
Vol 12 ◽  
pp. 175883592093615 ◽  
Author(s):  
Ding Ren ◽  
Hao Cheng ◽  
Xin Wang ◽  
Monika Vishnoi ◽  
Bin S. Teh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Difficult Problem ◽  
Therapeutic Strategies ◽  
Her2 Positive ◽  
Whole Brain Radiation ◽  
Breast Cancer Brain Metastasis

Systemic therapies for primary breast cancer have made great progress over the past two decades. However, oncologists confront an insidious and particularly difficult problem: in those patients with metastatic breast cancer, up to 50% of human epidermal growth factor 2 (HER2)-positive and 25–40% of triple-negative subtypes, brain metastases (BM) kill most of them. Fortunately, standard- of-care treatments for BM have improved rapidly, with a decline in whole brain radiation therapy and use of fractionated stereotactic radiosurgery as well as targeted therapies and immunotherapies. Meanwhile, advances in fundamental understanding of the basic biological processes of breast cancer BM (BCBM) have led to many novel experimental therapeutic strategies. In this review, we describe the most recent clinical treatment options and emerging experimental therapeutic strategies that have the potential to combat BCBM.

scholarly journals Appropriate treatment receipt after breast-conserving surgery

2018 ◽  
Vol 25 (6) ◽  
Author(s):  
K. Guidolin ◽  
M. Lock ◽  
K. Vogt ◽  
J. A. McClure ◽  
J. Winick-Ng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Standard Of Care ◽  
Breast Conserving Surgery ◽  
Income Quintile ◽  
Appropriate Treatment ◽  
Increased Risk ◽  
Breast Care ◽  
High Comorbidity ◽  
Incomplete Treatment ◽  
Treat Breast Cancer

Background Breast-conserving surgery (bcs) and radiation therapy (rt) are the standard of care for early breastcancer, although some women receive ipsilateral mastectomy or adjuvant tamoxifen, both of which can be appropriate alternatives to rt. Objectives of the present study were to determine the proportion of women who are treated appropriately after bcs and to identify factors associated with non-receipt of rt.Methods This retrospective cohort study used Ontario data linked at the Institute for Clinical and Evaluative Sciences to examine 33,718 patients who received bcs during 2004–2010. Primary outcome was rt receipt. The ipsilateral mastectomy rate and patient, surgeon, and setting variables were measured.Results Of the study patients, 86.1% received either rt or completion mastectomy; in the cohort less than 70 years of age, 90.8% received rt or completion mastectomy. Among patients less than 70 years of age, 3 risk factors for nonreceipt of rt were identified: age less than 46 years, treatment in a non-academic institution, and earlier year of initial bcs. Additionally, in the overall cohort, rt non-receipt was associated with high comorbidity, more than 40 km to the cancer centre, income quintile, and breast care specialization.Conclusions In Ontario, 90.8% of patients less than 70 years of age are appropriately treated for early breast cancer; approximately 1 in 10 do not receive rt or completion mastectomy. Based on those findings, women less than 46 years of age might be at increased risk of recurrence and death because of incomplete treatment. It also appears that academic centres more effectively treat breast cancer; however, breast cancer care appears to be improving over time in Ontario.

scholarly journals Case Report: Paclitaxel-Induced Pneumonitis in Early Breast Cancer: A Single Institution Experience and Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Luke Ardolino ◽  
Brandon Lau ◽  
Isabella Wilson ◽  
Julia Chen ◽  
Linda Borella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Confidence Interval ◽  
Early Breast Cancer ◽  
Predictive Biomarkers ◽  
Standard Of Care ◽  
Single Institution ◽  
Standard Of Care Treatment ◽  
Life Threatening ◽  
Key Questions

Taxane-based chemotherapy regimens are in widespread use as standard of care treatment for patients with early breast cancer, though rarely its use can be complicated by taxane-induced pneumonitis (TIP). While breast cancer is the most diagnosed cancer in women worldwide, TIP remains under-described in this setting. Key questions relate to its incidence, diagnosis and management, potential predictive biomarkers, and the balance between this life-threatening toxicity and curatively intended treatment. At a single Australian institution, 6 cases of TIP are identified among 132 patients treated with a paclitaxel-containing regimen for early breast cancer (4.55%, 95% confidence interval 1.69-9.63%). This review first outlines the presentation, management, and outcomes for these cases, then answers these questions and proposes an approach to suspected TIP in patients with breast cancer.

scholarly journals Should Genetic Testing for Cancer Predisposition Be Standard-of-Care for Women with Invasive Breast Cancer? The Murtha Cancer Center Experience

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 234 ◽  
Author(s):  
Seth K. Rummel ◽  
Leann A. Lovejoy ◽  
Clesson E. Turner ◽  
Craig D. Shriver ◽  
Rachel E. Ellsworth
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
High Risk ◽  
Invasive Breast Cancer ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Cancer Center ◽  
Clinical Testing ◽  
High Risk Women ◽  
Panel Testing

Currently, genetic testing is offered only to women diagnosed with breast cancer who meet a defined set of criteria and is not included as standard-of-care treatment at the time of diagnosis. Thus, a significant number of women diagnosed with breast cancer may miss the opportunity for precision medical treatment and risk management. The effects of eligibility, timing, and uptake of genetic testing were evaluated in a cohort of women with invasive breast cancer diagnosed between 2001–2018. Risk status was estimated using NCCN BRCA1/2 testing criteria and panel testing was performed for all women who had genomic DNA available. Of the 1231 women, 57.8% were eligible for genetic testing. Uptake of testing within high-risk women was 42.7% of which 6.6% pursued clinical testing only after a second tumor event. Mutation frequencies were 15.8%, 5.5%, and 4.0% in high-risk women with clinical testing, high-risk women without clinical testing, and low-risk women, respectively. More than 4% of all patients harbored pathogenic or likely pathogenic mutations detected only in the research setting. Inclusion of panel testing at the time of diagnosis would allow for appropriate surveillance and treatment strategies to be employed to reduce the risk of secondary tumors and improve patient outcome.

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