Harnessing the immune system in the battle against breast cancer

Nakasone, Elizabeth S.; Hurvitz, Sara A.; McCann, Kelly

doi:10.7573/dic.212520

Cited by 26 publications

(26 citation statements)

References 196 publications

(184 reference statements)

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“…Otherwise, PARP-1 and PARP-2 regulate several common inflammatory factors and cytokines including Tumor Necrosis Factor-α, inducible Nitric Oxide Synthase or Interleukin1-β suggesting The use of angiogenesis inhibition in combination with other treatments has been approved by the FDA in some scenarios; this is the case of an anti-VEGF specific antibody (bevacizumab, Avastin, Roche) used in combination with chemotherapy or different cytokines therapies for late-stage advanced metastatic cancers (including renal cell cancer, colorectal cancer, non-squamous non-small cell lung cancer and breast cancer) [79]. On the other hand, angiogenesis inhibitors in combination with immune checkpoint in the treatment of breast cancer showed no clear benefits and are still under evaluation, so there are no current FDA-approved indications for their use in breast cancer [80]. Current studies show how the combination of angiogenesis and PARP inhibitors will be likely safe due to non-overlapping toxicities, and it might be expected that PARP inhibitors could be used in this context at full mono-therapy dosages.…”

Section: Immuno-response Modulation By Parpmentioning

confidence: 99%

The Multifactorial Role of PARP-1 in Tumor Microenvironment

Martí

Fernández-Cortés

Serrano-Sáenz

et al. 2020

Cancers

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Poly(ADP-ribose) polymerases (PARPs), represent a family of 17 proteins implicated in a variety of cell functions; some of them possess the enzymatic ability to synthesize and attach poly (ADP-ribose) (also known as PAR) to different protein substrates by a post-translational modification; PARPs are key components in the cellular response to stress with consequences for different physiological and pathological events, especially during neoplasia. In recent years, using PARP inhibitors as antitumor agents has raised new challenges in understanding their role in tumor biology. Notably, the function of PARPs and PAR in the dynamic of tumor microenvironment is only starting to be understood. In this review, we summarized the conclusions arising from recent studies on the interaction between PARPs, PAR and key features of tumor microenvironment such as hypoxia, autophagy, tumor initiating cells, angiogenesis and cancer-associated immune response.

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Section: Immuno-response Modulation By Parpmentioning

confidence: 99%

The Multifactorial Role of PARP-1 in Tumor Microenvironment

Martí

Fernández-Cortés

Serrano-Sáenz

et al. 2020

Cancers

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“…to fatal distant diseases. In women with breast cancer, up to 30% node-negative cases and 70% of node-positive cases will recur [3].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Growth pattern can be used as a new characteristic to predict malignancy in breast cancer

Wang

Zhu

et al. 2020

Breast Cancer

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Background To date, anatomic tumor length is a key criterion for cancer staging and can be used to evaluate the effectiveness of therapies. This article describes growth pattern that can be used as a new characteristic to represent disease burden and tumor features and predict lymphatic metastasis. Methods Patients with breast cancer were included in this 10-year (1999-2008) hospital-based multicenter retrospective study. The pathologic length/height ratio was used to illustrate the correlation between tumor features, behaviors and treatments in breast malignancies. The most appropriate ratio was chosen based on the comprehensive evaluation of p value and changing trend of each characteristic. Results The sample consisted of 4211 women diagnosed with breast cancer. Among them, 2037 patients with complete pathologic length, width and height information were included in the final analysis. There were 2.34 ± 4.77 metastatic lymph nodes for spheroid tumors and 3.21 ± 5.82 for ellipsoid tumors when the cutoff point was 2. In addition, the proportion of ellipsoidal tumors gradually increased from 54.36 to 56.67% in the upper outer quadrant (UOQ) and from 6.7 to 9.03% in the central region with an increase in the cutoff point. The proportion of ER + PR + ellipsoid tumors significantly decreased from 50.1 to 45.35% and that of ER-PR ellipsoid tumors significantly increased from 32.73 to 36.24% with an increase in the cutoff point. Additionally, the best length/weight ratio to distinguish spheroid and ellipsoid tumors was 2. Conclusion This study described for the first time how growth pattern is correlated with tumor malignancy and how it influences the selection of therapeutic strategies for patients.

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“…Angiogenesis inhibitors and immune checkpoint inhibitors have thus far not reliably been shown to be of benefit in the treatment of breast cancer, and so there are no current FDA-approved indications for their use in breast cancer. 132 The combination of angiogenesis inhibitors and/or immune checkpoint inhibitors with PARP inhibitors will likely be safe due to nonoverlapping toxicities, and it might be expected that PARP inhibitors could be used at full monotherapy dosages.…”

Section: Combination Strategiesmentioning

confidence: 99%

Advances in the use of PARP inhibitor therapy for breast cancer

McCann¹,

Hurvitz²

2018

DIC

Self Cite

108

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Poly-ADP-ribose polymerase 1 (PARP-1) and PARP-2 are DNA damage sensors that are most active during S-phase of the cell cycle and that have wider-reaching roles in DNA repair than originally described. BRCA1 and BRCA2 (Breast Cancer) proteins are involved in homologous recombination repair (HRR), which requires a homologous chromosome or sister chromatid as a template to faithfully repair DNA double-strand breaks. The small-molecule NAD+ mimetics, olaparib, niraparib, rucaparib, veliparib, and talazoparib, inhibit the catalytic activity of PARP-1 and PARP-2 and are currently being studied in later-stage clinical trials. PARP inhibitor clinical trials have predominantly focused on patients with breast and ovarian cancer with deleterious germline BRCA1 and BRCA2 mutations (gBRCA1/2+) but are now expanding to include cancers with known, suspected, or more-likely-than-not defects in homologous recombination repair. In ovarian cancer, this group also includes women whose cancers are responsive to platinum therapy. Olaparib was FDA-approved in January 2018 for the treatment of gBRCA1/2+ metastatic breast cancers. gBRCA1+ predisposes women to develop triple-negative breast cancers, while women with gBRCA2+ tend to develop hormone-receptor-positive, human epidermal growth factor receptor 2 negative breast cancers. Although PARP inhibitor monotherapy strategies seem most effective in cancers with homologous recombination repair defects, combination strategies may allow expansion into a wider range of cancers. By interfering with DNA repair, PARP inhibitors essentially sensitize cells to DNA-damaging chemotherapies and radiation therapy. Certainly, one could also consider expanding the utility of PARP inhibitors beyond gBRCA1/2+ cancers by causing DNA damage with cytotoxic agents in the presence of a DNA repair inhibitor. Unfortunately, in numerous phase I clinical trials utilizing a combination of cytotoxic chemotherapy at standard doses with dose-escalation of PARP inhibitors, there has generally been failure to reach monotherapy dosages of PARP inhibitors due to myelosuppressive toxicities. Strategies utilizing angiogenesis inhibitors and immune checkpoint inhibitors are generally not hindered by additive toxicities, though the utility of combining PARP inhibitors with treatments that have not been particularly effective in breast cancers somewhat tempers enthusiasm. Finally, there are combination strategies that may serve to mitigate resistance to PARP inhibitors, namely, upregulation of the intracellular PhosphoInositide-3-kinase, AK thymoma (protein kinase B), mechanistic target of rapamycin (PI3K–AKT–mTOR) pathway, or perhaps are more simply meant to interfere with a cell growth pathway heavily implicated in breast cancers while administering relatively well-tolerated PARP inhibitor therapy.

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Harnessing the immune system in the battle against breast cancer

Cited by 26 publications

References 196 publications

The Multifactorial Role of PARP-1 in Tumor Microenvironment

The Multifactorial Role of PARP-1 in Tumor Microenvironment

Growth pattern can be used as a new characteristic to predict malignancy in breast cancer

Advances in the use of PARP inhibitor therapy for breast cancer

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