An evaluation of palbociclib as a breast cancer treatment option: a current update

Gallanis, Gregory T.; Pericas, Ramon I; Riegel, Anna T.; Pohlmann, Paula R.

doi:10.1080/14656566.2020.1838485

Cited by 5 publications

(3 citation statements)

References 66 publications

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“…This translates into better quality of life and postponement of need for chemotherapy. [5] The PFS and toxicity analysis results are consistent with other reports of routine clinical practice, that is, real-world evidence from India and other countries and the global clinical trials. [6][7][8][9][10][11][12][13][14][15][16][17] The observed OS is lower than reported in real-world studies and clinical trials.…”

Section: Discussionsupporting

confidence: 87%

Outcome in patients of hormone receptor (HR) positive (Her 2) negative metastatic breast cancer treated with palbociclib – A real-world experience

Bapna

Samar

Nag

et al. 2022

IJMIO

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Objectives: We present real-world outcome with the use of palbociclib in patients with HR-positive Her2-negative breast cancer treated at single center in India. Material and Methods: We conducted a medical audit of consecutive patients with HR-positive Her2-negative metastatic breast cancer, who were treated with palbociclib at our center between November 2016 and May 2020. Palbociclib was commenced at a dose of 125 mg orally once daily and a schedule of 21 days on therapy followed by 7 days off therapy was followed. Survival analysis included the Kaplan–Meier method using Statistical Package for the Social Sciences software (Version 26). HRs were calculated using Cox proportional hazard regression models and 95% confidence intervals (CIs) for the incidence estimates. Results: A total of 67 female patients were commenced on treatment with palbociclib between November 2016 and May 2020. The median age was 55 years (range 29–78 years). A total of 51 (76%) of these patients were postmenopausal and the remaining 16 were premenopausal. Baseline metastatic disease involved one organ/site in 23 (34%), two organs/sites in 32 (48%), three or more in 12 (18%). Bony metastasis alone was seen in 17 (25%) patients, visceral alone in 30 (45%), and the remaining 20 had both bony and visceral metastases. For these 67 patients, palbociclib was commenced as 1st line systemic therapy in 24 (36%) cases. Amongst the remaining 43 cases, it was 2nd line in 21 (31%); 3rd line and beyond in 22 (33%). Median PFS was 16.1 months (95% CI: 9.6–22.8) and median OS was 20.7 months (95% CI: 14.1–27.3). Median PFS for palbociclib use in first line was 18.7 months (95% CI: 4.6–32.9) while in subsequent lines, it was 13.8 months (95% CI: 9.8–17.9; log-rank P = 0.228). Median OS in patients who received palbociclib in first line was 23.2 months (95 % CI 20.1–26.3) and for those why received it in subsequent lines was 16.3 months (95 % CI: 12.5–20.1; P = 0.069). In total population, best response on imaging was CR in 11 (16%) cases (06 in 1st line setting and 05 in subsequent line setting); PR in 33 (49%); SD in 03; and progressive disease in 20. Median PFS with bone only metastasis: 20.9 months (95 % CI: 5.9–36.0), while with visceral metastasis 16.1 months (95% CI: 9.8–22.5; P = 0.537). Median OS with bone only metastasis: 22.7 months (95% CI: 17.8–27.5), while with visceral metastasis, it was 18.5 months (95% CI: 13.6–23.4; P = 0.314). Conclusion: Palbociclib is a useful addition in the management of HR +ve Her2 –ve breast cancer patients. Its benefit is confirmed in our real-world setting, both in the first and subsequent lines of therapy and the data are on similar lines as the global real-world data on palbociclib effectiveness.

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Section: Discussionsupporting

confidence: 87%

Outcome in patients of hormone receptor (HR) positive (Her 2) negative metastatic breast cancer treated with palbociclib – A real-world experience

Bapna

Samar

Nag

et al. 2022

IJMIO

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“…The primary major gene that was identified to be associated with hereditary BC in 1990 is BRCA1. Additionally, it was identified by employing linkage analysis in families by exploring suggestive pedigrees ( Gallanis et al, 2021 ). Following this, BRCA2 was mapped to chromosome 13 in 1994 ( Baldin et al, 1993 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting p53 misfolding conundrum by stabilizing agents and their analogs in breast cancer therapy: a comprehensive computational analysis

Haq,

Qayoom,

Sofi

et al. 2024

Front. Pharmacol.

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Cancer continues to be a major global public health concern and one of the foremost causes of death. Delays in the diagnosis and cure may cause an increase in advanced stage disease and mortality. The most common cancer found in women currently is breast carcinoma. Breast carcinoma has surpassed lung carcinoma and currently represents the chief type of cancer diagnosed (2.3 million new cases, which amount to 11.7% of all cancer cases). In addition, by 2040, the incidence will increase by more than 46% as per the estimates of GLOBOCAN. Triple-negative breast cancer (TNBC) represents a highly aggressive and invasive subtype of breast cancer, characterized by rapid progression, short response time to the available treatment, and poor clinical results. Thus, it is very crucial to develop novel diagnostic tools and therapeutics with good efficacy. A majority of cancers display malfunction along the p53 pathway. Moreover, p53 not only loses its function but is also prone to misfolding and aggregation, leading to formation of amyloid aggregates as well. Research is being carried out to find ways to restore the normal action and expression of p53. Here, we have explored PhiKan-083 for its possible stabilizing effect on p53 in order to address the problem with its misfolding. Thus, examining the analogs of PhiKan-083 that have a role in p53 stability will help update our understanding of cancer progression and may expedite the progress of new anticancer treatments. We anticipate that the drug molecules and their analogs targeting p53 aggregation may be used in combination with other anticancer compounds to solve the problem with p53 aggregation. In this study, by employing ADMET analysis, the compounds were screened, and we further examined the chosen compounds with the help of molecular docking. By using databases like UALCAN, TIMER, GEPIA, and PredictProtein, we investigated TP53’s expression pattern and prognostic relevance in various cancer settings.

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“…Herein, we show that EC cycle state and cell cycle regulatory genes are dysregulated in preclinical models of HHT induced by BMP9/10 blocking antibodies, as well as Alk1 genetic endothelial-specific inducible deletion in the Fucci (fluorescent ubiquitination-based cell cycle indicator) 2 cell cycle reporter mice. 9 Furthermore, we demonstrated that palbociclib, 10 a Food and Drug Administration–approved inhibitor of CDK (cyclin-dependent kinase) 4 and CDK6 currently used in clinical trials for breast cancer treatment, 11 prevents vascular malformations induced by both BMP9/10 blocking antibodies and endothelial-specific loss of Alk1 , referred to as Alk1 EC iKO (inducible knock-out). Mechanistically, we found that CDK4/6 inhibition-induced EC cycle arrest enables the expression of genes that collectively prevent the dysregulation of arteriovenous identity, migration, and metabolism, as well as genes regulating the VEGF-A and BMP9 signaling pathways, which are known to contribute to HHT pathogenesis.…”

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confidence: 99%

Induced Endothelial Cell Cycle Arrest Prevents Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia

Genet,

Paila

et al. 2024

Circulation

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BACKGROUND: Distinct endothelial cell cycle states (early G1 versus late G1) provide different “windows of opportunity” to enable the differential expression of genes that regulate venous versus arterial specification, respectively. Endothelial cell cycle control and arteriovenous identities are disrupted in vascular malformations including arteriovenous shunts, the hallmark of hereditary hemorrhagic telangiectasia (HHT). To date, the mechanistic link between endothelial cell cycle regulation and the development of arteriovenous malformations (AVMs) in HHT is not known. METHODS: We used BMP (bone morphogenetic protein) 9/10 blocking antibodies and endothelial-specific deletion of activin A receptor like type 1 ( Alk1 ) to induce HHT in Fucci (fluorescent ubiquitination-based cell cycle indicator) 2 mice to assess endothelial cell cycle states in AVMs. We also assessed the therapeutic potential of inducing endothelial cell cycle G1 arrest in HHT to prevent AVMs by repurposing the Food and Drug Administration–approved CDK (cyclin-dependent kinase) 4/6 inhibitor (CDK4/6i) palbociclib. RESULTS: We found that endothelial cell cycle state and associated gene expressions are dysregulated during the pathogenesis of vascular malformations in HHT. We also showed that palbociclib treatment prevented AVM development induced by BMP9/10 inhibition and Alk1 genetic deletion. Mechanistically, endothelial cell late G1 arrest induced by palbociclib modulates the expression of genes regulating arteriovenous identity, endothelial cell migration, metabolism, and VEGF-A (vascular endothelial growth factor A) and BMP9 signaling that collectively contribute to the prevention of vascular malformations. CONCLUSIONS: This study provides new insights into molecular mechanisms leading to HHT by defining how endothelial cell cycle is dysregulated in AVMs because of BMP9/10 and Alk1 signaling deficiencies, and how restoration of endothelial cell cycle control may be used to treat AVMs in patients with HHT.

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An evaluation of palbociclib as a breast cancer treatment option: a current update

Cited by 5 publications

References 66 publications

Outcome in patients of hormone receptor (HR) positive (Her 2) negative metastatic breast cancer treated with palbociclib – A real-world experience

Outcome in patients of hormone receptor (HR) positive (Her 2) negative metastatic breast cancer treated with palbociclib – A real-world experience

Targeting p53 misfolding conundrum by stabilizing agents and their analogs in breast cancer therapy: a comprehensive computational analysis

Induced Endothelial Cell Cycle Arrest Prevents Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia

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