Biologic Impact and Clinical Implication of mTOR Inhibition in Metastatic Breast Cancer

Westin, Gustavo Figueiredo Marcondes; Perez, Cesar A.; Wang, Emilie; Glück, Stefan

doi:10.5301/jbm.5000040

Cited by 4 publications

(5 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…123,125 In line, activation of mTOR was reported to promote acquired resistance to ET. 126 Westin et al 127 revealed association of mTOR activation to tamoxifen resistance. Also dysregulation of FOXO factors has emerged as key molecular feature of endocrine resistance 128 and a lack of FOXO3A expression in breast cancer patients is associated with increased recurrence rate.…”

Section: Growth Factor Signaling (Pi3k/akt/mtor/ Foxo)mentioning

confidence: 99%

Navigation through inter- and intratumoral heterogeneity of endocrine resistance mechanisms in breast cancer: A potential role for Liquid Biopsies?

et al. 2017

View full text Add to dashboard Cite

The majority of breast cancers are hormone receptor positive due to the expression of the estrogen and/or progesterone receptors. Endocrine therapy is a major treatment option for all disease stages of hormone receptor-positive breast cancer and improves overall survival. However, endocrine therapy is limited by de novo and acquired resistance. Several factors have been proposed for endocrine therapy failures, which include molecular alterations in the estrogen receptor pathway, altered expression of cell-cycle regulators, autophagy, and epithelial-to-mesenchymal transition as a consequence of tumor progression and selection pressure. It is essential to reveal and monitor intra- and intertumoral alterations in breast cancer to allow optimal therapy outcome. Endocrine therapy navigation by molecular profiling of tissue biopsies is the current gold standard but limited in many reasons. "Liquid biopsies" such as circulating-tumor cells and circulating-tumor DNA offer hope to fill that gap in allowing non-invasive serial assessment of biomarkers predicting success of endocrine therapy regimen. In this context, this review will provide an overview on inter- and intratumoral heterogeneity of endocrine resistance mechanisms and discuss the potential role of "liquid biopsies" as navigators to personalize treatment methods and prevent endocrine treatment resistance in breast cancer.

show abstract

Section: Growth Factor Signaling (Pi3k/akt/mtor/ Foxo)mentioning

confidence: 99%

Navigation through inter- and intratumoral heterogeneity of endocrine resistance mechanisms in breast cancer: A potential role for Liquid Biopsies?

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Through mTOR inhibition, temsirolimus stops cells from progressing from the G1 to the S phase of the cell cycle. It also inhibits mTOR-dependent protein translation, which is triggered by growth factor stimulation of cells, which has an impact on cell proliferation [24].…”

Section: Natural Macrocycles As Anti-renal Cell Cancer Agentsmentioning

confidence: 99%

From Rings to Remedies: Investigating the Structure-Activity Relationship of Macrocyclic Anticancer Agents

Rani,

Aslam,

Irfan

et al. 2024

Heterocyclic Chemistry - New Perspectives

View full text Add to dashboard Cite

The profound pharmacological attributes of macrocyclic compounds have spurred their transformation into pharmaceutical drugs. Within conformationally pre-organized ring structures, the macrocycle’s intricate functions and stereochemical complexity contribute to a heightened affinity and selectivity for protein targets. Simultaneously, they maintain sufficient bioavailability to penetrate intracellular locations. As a result, the construction of macrocycles emerges as an optimal strategy for addressing the challenge of “undruggable” targets like cancer. Cancer stands as the second most prevalent and formidable threat to human life, prompting researchers to channel their efforts toward the extraction and synthesis of effective therapeutic drugs designed on macrocyles to combat various types of cancer cells. Many macrocyclic drugs have been licensed by the Food and Drug Administration (FDA) for the treatment of cancer patients. Nonetheless, the significance of these compounds in the production of cancer therapeutics is still undervalued. According to recent research, macrocyclic compounds can be a useful tactic in the fight against drug resistance in the treatment of cancer. This chapter aims to present bits of evidence about the uses of macrocyclic compounds as potential cancer treatments. By providing more innovative approaches to aid cancer patients and society as a whole, this chapter will hopefully stimulate greater interest in the development of macrocyclic medicines for cancer therapy.

show abstract

“…It was approved to treat advanced renal cell carcinomas resistant to sunitinib or sorafenib in 2009 30 . Then in 2012, it was approved to use in combination with exemestane to treat advanced breast cancer that progressed on the treatment of letrozole or anastrozole 31 . It was also granted to treat neuroendocrine tumors, 32,33 and subependymal giant cell astrocytoma 34 in the past decade.…”

Section: Macrocyclic Compounds Targeting Cancer Developmentmentioning

confidence: 99%

“…30 Then in 2012, it was approved to use in combination with exemestane to treat advanced breast cancer that progressed on the treatment of letrozole or anastrozole. 31 It was also granted to treat neuroendocrine tumors, 32,33 and subependymal giant cell astrocytoma 34 in the past decade. Rapamycin was approved to treat facial angiofibroma associated with tuberous sclerosis in 2022.…”

Section: Macrocyclic Molecules That Inhibit Mtor Activitiesmentioning

confidence: 99%

Applications of macrocyclic molecules in cancer therapy: Target cancer development or overcome drug resistance

Song,

Wu,

et al. 2023

MedComm – Oncology

View full text Add to dashboard Cite

Cancer is a worldwide leading cause of cancer‐related death due to a lack of efficient disease control by drugs. With the increasing unmet needs in cancer treatment, developing novel effective cancer drugs is in great demand. Macrocyclic molecules represent a group of drug molecules with a cyclic skeleton which endows them with unique drug properties such as improved bioavailability, enhanced metabolic stability, increased binding affinity, and favorable pharmacokinetics parameters. The Food and Drug Administration (FDA) has approved a bunch of macrocyclic drugs to treat cancer patients. However, the importance of such molecules in cancer drug development remains underestimated. Recent studies support that macrocyclic molecules can also serve as an effective strategy to overcome drug resistance in cancer treatment, but is a lack of review. The purpose of this manuscript was to provide shreds of evidence on the applications of macrocyclic molecules for cancer therapy: (1) act as cancer drugs to target different proteins critical for cancer development; (2) act as cancer drugs to target resistant mutants of oncogenes to overcome drug resistance in targeted therapy. This review will help to attract more interest in developing macrocyclic drugs for cancer therapy and potentially provide more novel strategies to benefit cancer patients and society.

show abstract

Biologic Impact and Clinical Implication of mTOR Inhibition in Metastatic Breast Cancer

Cited by 4 publications

References 46 publications

Navigation through inter- and intratumoral heterogeneity of endocrine resistance mechanisms in breast cancer: A potential role for Liquid Biopsies?

Navigation through inter- and intratumoral heterogeneity of endocrine resistance mechanisms in breast cancer: A potential role for Liquid Biopsies?

From Rings to Remedies: Investigating the Structure-Activity Relationship of Macrocyclic Anticancer Agents

Applications of macrocyclic molecules in cancer therapy: Target cancer development or overcome drug resistance

Contact Info

Product

Resources

About