Everolimus-based combination therapies for HR+, HER2− metastatic breast cancer

O’Shaughnessy, Joyce; Beck, J. Thaddeus; Royce, Melanie

doi:10.1016/j.ctrv.2018.07.013

Cited by 52 publications

(32 citation statements)

References 77 publications

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“…The improvement was observed in both the multivariate and univariate analyses. For patients with ΔSUVmax less than 38%, an individualized treatment strategy could be recommended, such as increasing the dose of fulvestrant [32] or adding targeted drugs such as everolimus [33] or cyclin‐dependent kinase 4 and 6 inhibitors [34,35,36]. Currently, an imaging biomarker trial prospectively applying 18 F‐FES PET to guide therapy selection for patients with ER‐positive MBC is being performed at our center.…”

Section: Discussionmentioning

confidence: 99%

The Predictive Value of Early Changes in 18F-Fluoroestradiol Positron Emission Tomography/Computed Tomography During Fulvestrant 500 mg Therapy in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer

Cheng

Shi

et al. 2020

The Oncologist

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Background The aim of this study was to investigate the predictive value of early changes in 18F‐fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) during fulvestrant 500 mg therapy in patients with estrogen receptor (ER)‐positive metastatic breast cancer. Materials and Methods Patients underwent 18F‐FES PET/CT scans at both baseline (scan 1) and day 28 (scan 2). The maximum standardized uptake value (SUVmax) of all metastatic sites was determined in each scan, and the percentage reduction in SUVmax (ΔSUVmax) was calculated as [(SUVmax on scan 1‐SUVmax on scan 2)/ SUVmax on scan 1] * 100%. Results In total, 294 18F‐FES‐positive lesions from 36 patients were identified. The 18F‐FES SUVmax varied widely among lesions (median 5.7; range 1.8–32.4) and patients (median 5.1; range 2.5–13.2). After treatment, the median SUVmax among lesions and patients was 2.1 and 2.1, respectively. The ΔSUVmax ranged from −5.1% to 100%, with a median reduction of 61.3%. Using receiver operating characteristic analysis, the optimal cutoff point to discriminate patients who could derive clinical benefit from fulvestrant was determined to be 38.0%. Patients with a median ΔSUVmax ≥38.0% experienced significantly longer progression‐free survival (PFS) than those with ΔSUVmax <38.0% (28.0 months vs. 3.5 months, p = .003). Multivariate analysis demonstrated that ΔSUVmax ≥38.0% was an independent predictor of PFS benefit in patients receiving fulvestrant therapy. Conclusion Changes in SUVmax measured by serial imaging of 18F‐FES PET/CT could be used early to predict PFS benefit in patients receiving fulvestrant therapy. Implications for Practice The aim of this study was to evaluate the role of 18F‐fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) in predicting response to fulvestrant 500 mg therapy in patients with hormone receptor‐positive/human epidermal growth receptor 2–negative metastatic breast cancer. This study highlights the utility of FES PET/CT as a predictive factor to discriminate patients who might benefit from fulvestrant. Moreover, these findings showed that this molecular imaging technique might be a potential tool for physicians to make individualized treatment strategies.

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Section: Discussionmentioning

confidence: 99%

The Predictive Value of Early Changes in 18F-Fluoroestradiol Positron Emission Tomography/Computed Tomography During Fulvestrant 500 mg Therapy in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer

Cheng

Shi

et al. 2020

The Oncologist

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“…Everolimus has also been tested in cervical cancer cell lines with a remarkable ability to inactivate efficiently the HPV16 E7 oncoprotein inhibiting cell proliferation (202). The capacity of everolimus-based combinations to inhibit cell proliferation from several cancer types has been reported for breast cancer (203,204), renal cell carcinoma (205,206), and thyroid cancer (207) in clinical trials.…”

Section: Mtorc1 As a Therapeutic Targetmentioning

confidence: 99%

mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer

et al. 2019

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Continuous proliferation of tumor cells requires constant adaptations of energy metabolism to rapidly fuel cell growth and division. This energetic adaptation often comprises deregulated glucose uptake and lactate production in the presence of oxygen, a process known as the "Warburg effect." For many years it was thought that the Warburg effect was a result of mitochondrial damage, however, unlike this proposal tumor cell mitochondria maintain their functionality, and is essential for integrating a variety of signals and adapting the metabolic activity of the tumor cell. The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of numerous cellular processes implicated in proliferation, metabolism, and cell growth. mTORC1 controls cellular metabolism mainly by regulating the translation and transcription of metabolic genes, such as peroxisome proliferator activated receptor γ coactivator-1 α (PGC-1α), sterol regulatory element-binding protein 1/2 (SREBP1/2), and hypoxia inducible factor-1 α (HIF-1α). Interestingly it has been shown that mTORC1 regulates mitochondrial metabolism, thus representing an important regulator in mitochondrial function. Here we present an overview on the role of mTORC1 in the regulation of mitochondrial functions in cancer, considering new evidences showing that mTORC1 regulates the translation of nucleus-encoded mitochondrial mRNAs that result in an increased ATP mitochondrial production. Moreover, we discuss the relationship between mTORC1 and glutaminolysis, as well as mitochondrial metabolites. In addition, mitochondrial fission processes regulated by mTORC1 and its impact on cancer are discussed. Finally, we also review the therapeutic efficacy of mTORC1 inhibitors in cancer treatments, considering its use in combination with other drugs, with particular focus on cellular metabolism inhibitors, that could help improve their anti neoplastic effect and eliminate cancer cells in patients. de la Cruz López et al. mTORC1 and Mitochondrial Functions Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The handling editor declared a shared affiliation, though no other collaboration, with with several of the authors AG and KC.

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“…Furthermore, due to their complex and not deeply understood mechanisms of action, CDKis, especially abemaciclib, have shown as monotherapy encouraging results in preclinical models of other tumor such as glioblastoma, non-small cell lung cancer, head and neck squamous cell carcinoma, pancreatic cancer, esophageal adenocarcinoma, melanoma, colon cancer, myeloma, and ovarian cancer [ 113 , 161 , 162 ]. Analogously, since CDKis influence a wide range of key functional proteins, several studies have investigated possible therapeutic strategies combining CDKis to drugs targeting immune checkpoint such as PD-1/PD-L1 [ 163 , 164 ], or other molecules interacting with the PI3K-AKT-mTOR pathway [ 165 , 166 ].…”

Section: Discussionmentioning

confidence: 99%

CDK4/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions

Roncato

Angelini

Pani

et al. 2020

IJMS

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Palbociclib, ribociclib, and abemaciclib belong to the third generation of cyclin-dependent kinases inhibitors (CDKis), an established therapeutic class for advanced and metastatic breast cancer. Interindividual variability in the therapeutic response of CDKis has been reported and some individuals may experience increased and unexpected toxicity. This narrative review aims at identifying the factors potentially concurring at this variability for driving the most appropriate and tailored use of CDKis in the clinic. Specifically, concomitant medications, pharmacogenetic profile, and pathophysiological conditions could influence absorption, distribution, metabolism, and elimination pharmacokinetics. A personalized therapeutic approach taking into consideration all factors potentially contributing to an altered pharmacokinetic/pharmacodynamic profile could better drive safe and effective clinical use.

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Everolimus-based combination therapies for HR+, HER2− metastatic breast cancer

Cited by 52 publications

References 77 publications

The Predictive Value of Early Changes in 18F-Fluoroestradiol Positron Emission Tomography/Computed Tomography During Fulvestrant 500 mg Therapy in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer

The Predictive Value of Early Changes in 18F-Fluoroestradiol Positron Emission Tomography/Computed Tomography During Fulvestrant 500 mg Therapy in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer

mTORC1 as a Regulator of Mitochondrial Functions and a Therapeutic Target in Cancer

CDK4/6 Inhibitors in Breast Cancer Treatment: Potential Interactions with Drug, Gene, and Pathophysiological Conditions

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