Autophagy and senescence facilitate the development of antiestrogen resistance in ER positive breast cancer DOI Creative Commons

Michael K. McGrath,

Ali Abolhassani,

Luke Guy

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: March 18, 2024

Estrogen receptor positive (ER + ) breast cancer is the most common diagnosed annually in US with endocrine-based therapy as standard-of-care for this subtype. Endocrine includes treatment antiestrogens, such selective estrogen modulators (SERMs), downregulators (SERDs), and aromatase inhibitors (AIs). Despite appreciable remission achievable these treatments, a substantial cohort of women will experience primary tumor recurrence, subsequent metastasis, eventual death due to their disease. In cases, cells have become resistant endocrine therapy, resistance identified major obstacle medical oncologist patient. To combat development resistance, options ER , HER2 negative now include CDK4/6 used adjuvants antiestrogen treatment. addition dysregulated activity CDK4/6, plethora genetic biochemical mechanisms been that contribute resistance. These mechanisms, which by lab-based studies utilizing appropriate cell animal models cancer, clinical gene expression profiles identify candidate genes, are subject review. addition, we discuss molecular targeting strategies utilized conjunction or target cells. Of approaches currently being explored improve efficacy patient outcome, two adaptive survival autophagy, “reversible” senescence, considered targets. Autophagy and/or senescence induction response treatments often induced inhibitors. Unfortunately, effective pathways not yet successfully developed. Thus, there an urgent need continued interrogation autophagy clinically relevant long-term goal identifying new targets improved cancer.

Language: Английский

The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis DOI Creative Commons
Kay‐Dietrich Wagner, Nicole Wagner

Cells, Journal Year: 2022, Volume and Issue: 11(12), P. 1966 - 1966

Published: June 19, 2022

It is widely accepted that senescent cells accumulate with aging. They are characterized by replicative arrest and the release of a myriad factors commonly called senescence-associated secretory phenotype. Despite cell cycle arrest, these metabolically active functional. The SASP mostly thought to cause tissue dysfunction induce senescence in surrounding cells. As major markers for aging senescence, p16INK4, p14ARF/p19ARF, p21 established. Importantly, also implicated development, cancer, homeostasis. While many have been identified, none able unambiguously identify all However, increased levels cyclin-dependent kinase inhibitors p16INK4A often used phenotypes. We review here knowledge p16INK4A, embryonic postnatal development potential functions pathophysiology establishment senolytic therapies ultimate goal improve healthy requires care detailed about involvement proteins developmental processes homeostatic mechanism. contributes topics, summarizes open questions, provides some directions future research.

Language: Английский

Citations

79
Emerging role of aging in the progression of NAFLD to HCC DOI
Yongyuan He,

Yinghong Su,

Chengcheng Duan

et al.

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 84, P. 101833 - 101833

Published: Dec. 22, 2022

Language: Английский

Citations

45
Molecular Mechanisms of Western Diet-Induced Obesity and Obesity-Related Carcinogenesis—A Narrative Review DOI Creative Commons

Dhruvi Lathigara,

Devesh Kaushal, Robert Wilson

et al.

Metabolites, Journal Year: 2023, Volume and Issue: 13(5), P. 675 - 675

Published: May 21, 2023

The present study aims to provide a narrative review of the molecular mechanisms Western diet-induced obesity and obesity-related carcinogenesis. A literature search Cochrane Library, Embase Pubmed databases, Google Scholar grey was conducted. Most that induce are also involved in twelve Hallmarks Cancer, with fundamental process being consumption highly processed, energy-dense diet deposition fat white adipose tissue liver. generation crown-like structures, macrophages surrounding senescent or necrotic adipocytes hepatocytes, leads perpetual state chronic inflammation, oxidative stress, hyperinsulinaemia, aromatase activity, activation oncogenic pathways loss normal homeostasis. Metabolic reprogramming, epithelial mesenchymal transition, HIF-1α signalling, angiogenesis host immune-surveillance particularly important. Obesity-associated carcinogenesis is closely related metabolic syndrome, hypoxia, visceral dysfunction, oestrogen synthesis detrimental cytokine, adipokine exosomal miRNA release. This important pathogenesis oestrogen-sensitive cancers, including breast, endometrial, ovarian thyroid cancer, but ‘non-hormonal’ obesity-associated cancers such as cardio-oesophageal, colorectal, renal, pancreatic, gallbladder hepatocellular adenocarcinoma. Effective weight interventions may improve future incidence overall cancer.

Language: Английский

Citations

33
Cellular senescence in asthma: from pathogenesis to therapeutic challenges DOI Creative Commons
Rongjun Wan, Prakhyath Srikaram,

Vineeta Guntupalli

et al.

EBioMedicine, Journal Year: 2023, Volume and Issue: 94, P. 104717 - 104717

Published: July 11, 2023

Asthma is a heterogeneous chronic respiratory disease that impacts nearly 10% of the population worldwide. While cellular senescence normal physiological process, accumulation senescent cells considered trigger transforms physiology into pathophysiology tissue/organ. Recent advances have suggested significance in asthma. With this review, we focus on literature regarding and stress responses link triggers asthma to senescence, including telomere shortening, DNA damage, oncogene activation, oxidative-related senescence-associated secretory phenotype (SASP). The association phenotypes, airway inflammation remodeling, was also reviewed. Importantly, several approaches targeting such as senolytics senomorphics, emerged promising strategies for treatment. Therefore, might represent mechanism asthma, senescence-related molecules pathways could be targeted therapeutic benefit.

Language: Английский

Citations

33
A cross-talk between sestrins, chronic inflammation and cellular senescence governs the development of age-associated sarcopenia and obesity DOI
Gregory Livshits, Alexander Kalinkovich

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 86, P. 101852 - 101852

Published: Jan. 13, 2023

Language: Английский

Citations

29
Hallmarks of Cancer Affected by the MIF Cytokine Family DOI Open Access
Romina Mora Barthelmess, Benoı̂t Stijlemans, Jo A. Van Ginderachter

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(2), P. 395 - 395

Published: Jan. 6, 2023

New diagnostic methods and treatments have significantly decreased the mortality rates of cancer patients, but further improvements are warranted based on identification novel tumor-promoting molecules that can serve as therapeutic targets. The macrophage migration inhibitory factor (MIF) family cytokines, comprising MIF DDT (also known MIF2), overexpressed in almost all types, their high expressions related to a worse prognosis for patients. is involved 9 10 hallmarks cancer, its inhibition by antibodies, nanobodies, or small synthetic has shown promising results. Even though also proposed be several available information about pro-tumoral role mechanism action more limited. Here, we provide an overview involvement both propose blocking cytokines needed obtain maximum anti-tumor response.

Language: Английский

Citations

28
Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells DOI Open Access

Youssef Al Hmada,

Robert T. Brodell,

Naji Kharouf

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 470 - 470

Published: Jan. 22, 2024

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize distant organs. a heterogeneous tumor, composed genetically divergent subpopulations, including small fraction melanoma-initiating cancer stem-like cells (CSCs) many non-cancer stem (non-CSCs). CSCs are their unique surface proteins associated with aberrant signaling pathways causal or consequential relationship tumor progression, drug resistance, recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, NF1). Of these, BRAF NRAS oncogenes, 50% melanomas demonstrating mutation (BRAF

Language: Английский

Citations

15
Epigenetic regulations of cellular senescence in osteoporosis DOI
Shaochuan Huo,

Xinzheng Tang,

Weijian Chen

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102235 - 102235

Published: Feb. 16, 2024

Language: Английский

Citations

12
Cellular senescence in cancer: molecular mechanisms and therapeutic targets DOI Creative Commons
Ping Jin,

Xirui Duan,

Lei Li

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: April 24, 2024

Abstract Aging exhibits several hallmarks in common with cancer, such as cellular senescence, dysbiosis, inflammation, genomic instability, and epigenetic changes. In recent decades, research into the role of senescence on tumor progression has received widespread attention. While how limits course cancer is well established, also been found to promote certain malignant phenotypes. The tumor‐promoting effect mainly elicited by a senescence‐associated secretory phenotype, which facilitates interaction senescent cells their surroundings. Targeting therefore offers promising technique for therapy. Drugs that pharmacologically restore normal function or eliminate them would assist reestablishing homeostasis cell signaling. Here, we describe its occurrence, impact biology. A “one‐two‐punch” therapeutic strategy first induced, followed use senotherapeutics eliminating introduced. advances application targeting treatment are outlined, an emphasis drug categories, strategies screening, design, efficient targeting. This work will foster thorough comprehension encourage additional within this field.

Language: Английский

Citations

12
Understanding the intricacies of cellular senescence in atherosclerosis: Mechanisms and therapeutic implications DOI Creative Commons
Ilyas Ali, Hongliang Zhang, Syed Aqib Ali Zaidi

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102273 - 102273

Published: March 14, 2024

Language: Английский

Citations

11