Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: April 12, 2022

Abstract Triple-negative breast cancer (TNBC) is a subtype of human with one the worst prognoses, no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed (PCD), has been widely reported to have numerous links progression and therapy many types cancer. Of note, RCD can be divided into different subroutines, including autophagy-dependent death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis anoikis. More recently, targeting subroutines small-molecule compounds emerging promising strategy, which rapidly progressed in treatment TNBC. Therefore, this review, we focus on summarizing molecular mechanisms above-mentioned seven major related TNBC latest progress subroutines. Moreover, further discuss combined drug (e.g., narciclasine) or more drugs torin-1 chloroquine) achieve potential by regulating importantly, demonstrate several ONC201 NCT03733119) clinical trials. Taken together, these findings will provide clue illuminating actionable low-hanging-fruit druggable targets candidate for RCD-related therapies. Graphical abstract

Language: Английский

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International variation in breast cancer incidence and mortality in young women

Breast Cancer Research and Treatment, Journal Year: 2020, Volume and Issue: 186(2), P. 497 - 507

Published: Nov. 3, 2020

Language: Английский

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Trajectories of fear of cancer recurrence in young breast cancer survivors

Cancer, Journal Year: 2021, Volume and Issue: 128(2), P. 335 - 343

Published: Oct. 6, 2021

Background Fear of cancer recurrence (FCR) is more intense in younger women. Because FCR a powerful determinant quality life, identifying those at risk for persistently elevated can inform timing interventions. Methods A total 965 women with stage 0 to III breast enrolled the Young Women's Breast Cancer Study, prospective cohort diagnosed age ≤40 years, completed 3‐item Lasry Recurrence Index. Group‐based trajectory modeling was used classify distinct patterns from baseline through 5 years post‐diagnosis. Multinomial logistic regression identify patient, disease, and treatment characteristics associated each trajectory. Results Five trajectories were identified majority participants having moderate (33.1%) or high (27.6%) that improved over time. 6.9% had worsened, whereas 21.7% remained throughout. In fully adjusted multinomial model, stages II (vs I) higher odds being high/stable trajectory, I), financially comfortable not comfortable), lower White non‐White) Conclusions Although improves time many young cancer, approximately one‐third severe did improve worsened after diagnosis. Ongoing monitoring warranted, early referral mental health professionals indicated highest unresolved FCR. Lay Summary common among cancer. The authors followed large when they 40 younger, found show fears do always may require targeted intervention.

Language: Английский

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The impact of young age at diagnosis (age <40 years) on prognosis varies by breast cancer subtype: A U.S. SEER database analysis

The Breast, Journal Year: 2021, Volume and Issue: 61, P. 77 - 83

Published: Dec. 13, 2021

Women under 40 years old are at increased risk for developing human epidermal growth factor receptor 2 (HER2) positive or triple negative subtype and more advanced breast cancer, yet young age itself has also historically been an independent prognostic factor.Using the Surveillance, Epidemiology, End Results (SEER) Program, we examined data 271,173 women with stage I-III cancer between 2010 2015. Using Fine Gray regression models to account competing risks, of cancer-specific death by clinical subtypes, considering grade, hormone (HR) HER2 status, adjusting demographic, treatment variables.Of eligible analysis, 14,109 were <40 age. likely be non-white, uninsured, have higher stage, HER2-positive triple-negative disease (all, p < 0.001). Compared ages 40-60, had mortality (hazard ratio, 1.8; 95% confidence interval (CI) 1.6-1.9) in unadjusted analysis. In controlling factors, was significantly associated among HR-positive, lower grade ratio 1.7; CI 1.4-2.1) but not high grade/HR-positive, HER2-positive, disease. >75 all subtypes.With modern subtyping, remains independently worse outcomes 30 months follow-up only

Language: Английский

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Involvement in Tumorigenesis and Clinical Significance of CXCL1 in Reproductive Cancers: Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer and Prostate Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7262 - 7262

Published: April 14, 2023

C-X-C motif chemokine ligand 1 (CXCL1) is a member of the CXC subfamily and for CXCR2. Its main function in immune system chemoattraction neutrophils. However, there lack comprehensive reviews summarizing significance CXCL1 cancer processes. To fill this gap, work describes clinical participation processes most important reproductive cancers: breast cancer, cervical endometrial ovarian prostate cancer. The focus on both aspects molecular We describe association with features tumors, including prognosis, ER, PR HER2 status, TNM stage. present contribution to chemoresistance radioresistance selected tumors its influence proliferation, migration, invasion tumor cells. Additionally, we impact microenvironment cancers, effect angiogenesis, recruitment, cancer-associated cells (macrophages, neutrophils, MDSC, Treg). article concludes by introducing drugs targeting CXCL1. This paper also discusses ACKR1/DARC cancers.

Language: Английский

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H-CNN combined with tissue Raman spectroscopy for cervical cancer detection

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy, Journal Year: 2023, Volume and Issue: 291, P. 122339 - 122339

Published: Jan. 12, 2023

Language: Английский

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Capturing breast cancer subtypes in cancer registries: insights into real-world incidence and survival

Journal of Cancer Policy, Journal Year: 2025, Volume and Issue: unknown, P. 100567 - 100567

Published: March 1, 2025

Breast cancer treatment is guided by diagnostic subtyping, yet registries do not routinely capture this information, and real-world studies reporting subtype-specific incidence survival reflect contemporary clinical management. We analysed breast using Queensland registry data (2017-2019), stratifying hormone receptor (HR) HER2 status. Subtype-specific, age-standardised rates were: 125.6 HR+/HER2- cases/100,000 women (76.0% of all diagnoses), followed 17.7/100,000 for triple-negative (TNBC; 10.3%), 15.0/100,000 HR+/HER2+ (8.7%), 8.6/100,000 HR-/HER2+ (5.0%). Compared to HR+/HER2-, other subtypes had poorer cancer-specific (BCSS) overall (OS; except OS) at 2-years, with OS associations attenuated but still significant TNBC 4-years. Stratifying stage diagnosis, consistently 2-year BCSS in those I-III (HRadj>7), marginally IV. the most common subtype has best short-term prognosis. markedly survival, even when diagnosed an early stage. This study provides benchmarking highlights importance capturing status surveillance. Routinely stages needs be prioritised assess efficacy evolving targeted therapies inform tailored surveillance high-risk subtypes.

Language: Английский

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Effects of marital status on breast cancer survival by age, race, and hormone receptor status: A population‐based Study

Cancer Medicine, Journal Year: 2019, Volume and Issue: 8(10), P. 4906 - 4917

Published: July 2, 2019

Abstract Introduction It remains unclear whether marital status could affect the breast cancer‐caused special survival (BCSS) of patients with cancer. Therefore, we sought to explore influence demographic and pathological factors on prognosis Materials methods We selected meeting eligibility criteria from Surveillance, Epidemiology, End Results (SEER) cancer registry program. assessed effect overall (OS) BCSS using Kaplan‐Meier curve multivariate Cox proportional hazards regression. Compared divorced/separated/widowed (DSW) patients, married (AHR 0.7483, 95% CI: 0.729‐0.7682, P < 0.001) single had better 0.9096, 0.8796‐0.9406, 0.001). Married kept among all age subgroups, while occurred only in groups older than 35 years. As for race hormone receptor (HRs), was observed white 0.881, 0.8457‐0.9177, ER+/PR + 0.8844, 0.8393‐0.932, Conclusion Our findings demonstrated that their DSW counterparts. Age, race, HRs correlation between BCSS.

Language: Английский

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Prognostic Impact of the 21-Gene Recurrence Score Assay Among Young Women With Node-Negative and Node-Positive ER-Positive/HER2-Negative Breast Cancer

Journal of Clinical Oncology, Journal Year: 2019, Volume and Issue: 38(7), P. 725 - 733

Published: Dec. 6, 2019

The 21-gene recurrence score (RS) assay is prognostic among women with early-stage estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer used to inform recommendations for chemotherapy. Women ≤ 40 years of age represent a minority patients studied using gene expression profiles.The Young Women's Breast Cancer Study prospective cohort diagnosed at enrolled between 2006 2016 (N = 1,302). We identified stage I-III ER+/HER2- cancer. RS was performed on banked specimens who had not been tested clinically. Distant recurrence-free survival (DRFS) assessed by TAILORx traditional risk groups axillary node-negative (N0) limited node-positive (N1) cancer.Among eligible 577), 189 (33%) undergone testing, 320 (56%) sufficient testing. Median follow-up 6.0 years. diagnosis 37.2 years; 300 509 (59%) N0 cancer, whom 195 (65%) an 11-25 fewer than half (86 195; 44%) received Six-year DRFS rates were 94.4% 92.3% (RS < 11), 96.9% 85.2% 11-25), 85.1% 71.3% ≥ 26) N1 disease, respectively.The young representing valuable tool stratification. Disease outcomes median 6 disease 0-25, chemotherapy, 11 very good, whereas those 26 or experienced substantial early distant recurrence.

Language: Английский

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In modern times, how important are breast cancer stage, grade and receptor subtype for survival: a population-based cohort study

Breast Cancer Research, Journal Year: 2021, Volume and Issue: 23(1)

Published: Feb. 1, 2021

Abstract Background In breast cancer, immunohistochemistry (IHC) subtypes, together with grade and stage, are well-known independent predictors of cancer death. Given the immense changes in treatment survival over time, we used recent population-based data to test combined influence IHC stage on Methods We identified 24,137 women invasive aged 20 74 between 2005 2015 database Cancer Registry Norway. Kaplan-Meier curves, mortality rates adjusted hazard ratios for death were estimated by grade, tumour size nodal status during 13 years follow-up. Results Within all When combining prognostic factors, risk was 20- 40-fold higher worst groups compared group smallest size, low ER+PR+HER2− status. Among node-negative ER+HER2− tumours, larger conferred a significantly increased mortality. ER+PR−HER2− tumours high advanced showed particularly similar TNBC. examining early versus late mortality, explained most (> 5 years) among ER+ subtypes. Conclusions There is wide range risks dying from also across small low/intermediate tumours. Thus, even modern treatment, molecular subtype (reflected subtypes) matter prognosis.

Language: Английский

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