Angiotensin-(1-7) inhibits triple negative tumor growth through the inhibition of angiogenesis and a reduction in placental growth factor PlGF.

Triple negative breast cancer (TNBC) is a very aggressive type of cancer. TNBC is not just a single type of disease to be cured, but it consists of 6 subtypes which are basal-like 1 and 2, immunomodulatory, mesenchymal, mesenchymal stem- like and luminar androgen receptor. These subtypes has diverse characteristics, which hold potential opportunity for targeted treatment. Lack of molecular targets for triple negative tumor lead to limited targeted therapies for TNBC. Therefore, effective targeted therapies are urgently needed for TNBC. This paper will highlight on the potential targets in TNBC and treatment options that are currently under clinical application.

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Retrospective comparisons of nanoparticle albumin-bound paclitaxel and docetaxel neoadjuvant regimens for breast cancer

Nanomedicine ◽

10.2217/nnm-2020-0458 ◽

2021 ◽

Vol 16 (5) ◽

pp. 391-400

Author(s):

Yan Li ◽

Xiang Chen ◽

Qiannan Zhu ◽

Rui Chen ◽

Lu Xu ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Pathological Complete Response ◽

Response Rates ◽

Complete Response ◽

Neoadjuvant Systemic Therapy ◽

Triple Negative Tumor ◽

Negative Tumor ◽

Dose Dense ◽

Peripheral Sensory

Aim: To compare the efficacy and safety of 2-weekly nanoparticle albumin-bound paclitaxel (nP) and 3-weekly docetaxel regimens as neoadjuvant systemic therapy (NST) for breast cancer. Materials & methods: Patients (n = 201) received NST comprising either dose-dense epirubicin and cyclophosphamide followed by 2-weekly nP (n = 104) or 3-weekly courses of epirubicin and cyclophosphamide followed by docetaxel (n = 97). Results: Higher pathological complete response rates were achieved by the nP group. Subgroup analysis showed that the nP-based regimen achieved higher pathological complete response rates in patients with triple-negative tumor cells and high Ki67 levels. However, grades 3–4 peripheral sensory neuropathies were more frequent in the nP group. Conclusion: The 2-weekly nP-based regimen might be a better choice of NST for patients with breast cancer.

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MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition

Journal of Experimental Medicine ◽

10.1084/jem.20111512 ◽

2012 ◽

Vol 209 (4) ◽

pp. 679-696 ◽

Cited By ~ 197

Author(s):

Dai Horiuchi ◽

Leonard Kusdra ◽

Noelle E. Huskey ◽

Sanjay Chandriani ◽

Marc E. Lenburg ◽

...

Keyword(s):

Triple Negative ◽

Tumor Regression ◽

Breast Tumors ◽

Breast Cancers ◽

Her2 Receptor ◽

Altered Expression ◽

Synthetic Lethal ◽

Pathway Activation ◽

Triple Negative Tumor ◽

Negative Tumor

Estrogen, progesterone, and HER2 receptor-negative triple-negative breast cancers encompass the most clinically challenging subtype for which targeted therapeutics are lacking. We find that triple-negative tumors exhibit elevated MYC expression, as well as altered expression of MYC regulatory genes, resulting in increased activity of the MYC pathway. In primary breast tumors, MYC signaling did not predict response to neoadjuvant chemotherapy but was associated with poor prognosis. We exploit the increased MYC expression found in triple-negative breast cancers by using a synthetic-lethal approach dependent on cyclin-dependent kinase (CDK) inhibition. CDK inhibition effectively induced tumor regression in triple-negative tumor xenografts. The proapoptotic BCL-2 family member BIM is up-regulated after CDK inhibition and contributes to this synthetic-lethal mechanism. These results indicate that aggressive breast tumors with elevated MYC are uniquely sensitive to CDK inhibitors.

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Dual targeting of vascular endothelial growth factor and bone morphogenetic protein-9/10 impairs tumor growth through inhibition of angiogenesis

Cancer Science ◽

10.1111/cas.13103 ◽

2017 ◽

Vol 108 (1) ◽

pp. 151-155 ◽

Cited By ~ 4

Author(s):

Yuichi Akatsu ◽

Yasuhiro Yoshimatsu ◽

Taishi Tomizawa ◽

Kazuki Takahashi ◽

Akihiro Katsura ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Tumor Growth ◽

Bone Morphogenetic Protein ◽

Vascular Endothelial ◽

Dual Targeting ◽

Morphogenetic Protein ◽

Inhibition Of Angiogenesis ◽

Bone Morphogenetic Protein 9 ◽

Endothelial Growth Factor

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Placental growth factor supports neuroendocrine tumor growth and predicts disease prognosis in patients

Endocrine Related Cancer ◽

10.1530/erc-12-0223 ◽

2013 ◽

Vol 20 (3) ◽

pp. 305-319 ◽

Cited By ~ 17

Author(s):

Georg Hilfenhaus ◽

Andreas Göhrig ◽

Ulrich-Frank Pape ◽

Tabea Neumann ◽

Henning Jann ◽

...

Keyword(s):

Growth Factor ◽

Tumor Growth ◽

Antiangiogenic Therapy ◽

Placental Growth Factor ◽

Low Grade ◽

Advanced Tumor ◽

And Migration ◽

Proliferation And Migration

Placental growth factor (PlGF), a VEGF-homolog implicated in tumor angiogenesis and adaptation to antiangiogenic therapy, is emerging as candidate target in malignancies. Here, we addressed the expression, function, and prognostic value of PlGF in neuroendocrine tumors (NETs). PlGF was determined in NET patients' sera collected retrospectively (n=88) and prospectively (n=87) using Roche-Elecsys and correlated with clinicopathological data. Tumoral PlGF was evaluated by immunohistochemistry, effects of PlGF on proliferation and migration in vitro were assessed using different NET cell lines and effects on tumor growth in vivo in orthotopic xenografts. Circulating and tumoral PlGF was elevated in patients with pancreatic NETs (pNETs) compared with control sera and respective healthy tissue. De novo PlGF expression occurred primarily in the tumor stroma, suggesting paracrine stimulatory circuits. Indeed, PlGF enhanced NET proliferation and migration in vitro and, conversely, neutralizing antibodies to PlGF reduced tumor growth in vivo. Elevated circulating PlGF levels in NET patients correlated with advanced tumor grading and were associated with reduced tumor-related survival in pNETs. Subsequent determinations confirmed and extended our observation of elevated PlGF levels in a prospective cohort of grade 1 and grade 2 pNETs (n=30) and intestinal NETs (n=57). In low-grade pNETs, normal circulating PlGF levels were associated with better survival. In intestinal NETs, circulating PlGF above median emerged as an independent prognostic factor for shorter time-to-progression in multivariate analyses. These data assign to PlGF a novel function in the pathobiology of NETs and propose PlGF as a prognostic parameter and therapeutic target.

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Prognosis of pT1a,bN0 breast cancer: Perception from the French oncology community—Results from the EURISTIC survey.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e11607 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e11607-e11607

Author(s):

Marc Spielmann ◽

David Azria ◽

Jean Marc Classe ◽

Florence Dalenc ◽

Clarisse Dromain ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Size ◽

Perceived Risk ◽

Triple Negative ◽

Early Stage ◽

Tumour Size ◽

Tumor Biology ◽

Her2 Positive ◽

Triple Negative Tumor ◽

Negative Tumor

e11607 Background: Although most early-stage breast tumors have a favourable outcome, some subgroups carry a higher recurrence risk. The objective of the EURISTIC Survey was to evaluate the perception French physicians have of the prognostic risk associated with the biopathological characteristics of tumors in pT1a,b N0 breast cancer. Methods: This 38 item postal survey was developed by an expert panel. 2,000 physicians involved in breast cancer treatment were contacted. Specialities involved were medical and radiation oncologists, surgeons, radiologists and pathologists. Results: The survey was conducted between September and December 2012. A total of 663 physicians responded (response rate = 33%). They stated treating an average of 50 breast cancer patients per month. 58% of physicians reported that tumour size was not considered a major parameter in this clinical setting. In the absence of an adjuvant treatment, the prognosis of T1a,bN0 carcinoma was perceived better if HR-positive rather than HER2-positive or triple-negative with a "positive" prognosis perception rated by 83%, 21% and 8% of physicians respectively. For pT1a,bN0 tumors, the criteria with the highest perceived prognostic risk were ranked as follows: HER2+ (29%), HR- (20%) elevated tumor grade (20%) and triple negative tumor (14%). The average size threshold for a "negative" prognostic rated tumor was 18 mm. This threshold was scaled up for HR-positive carcinoma (22 mm) and scaled down for HER2-positive (10mm) or triple negative carcinoma (7mm). Between 4 and 17 mm, there was a linear correlation between tumor size and perceived risk of recurrence with HER2-positive tumors always carrying a worse prognostic than HR-positive tumor (Table). Conclusions: French physicians have the perception that HER2-positivity and triple negative tumor biology strongly impact the prognosis of pT1a,b N0 carcinoma, independent of tumor size. [Table: see text]

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