Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Май 7, 2024

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer more challenging and may be unresponsive to conventional therapy. Immunotherapy crucial for treating but its resistance a major limitation. tumor microenvironment (TME) vital in modulating immunotherapy response. Various microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), are involved TME modulation cause resistance. This review highlights role stromal microenvironment, including involvement CAF-TAM interaction, alteration metabolism leading failure, other latest strategies, high throughput genomic screening, single-cell spatial omics techniques identifying immune genes regulating emphasizes therapeutic approach overcome through CAF reprogramming, TAM polarization, metabolism, alterations.

Язык: Английский

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Research progress in tumor angiogenesis and drug resistance in breast cancer

Cancer Biology and Medicine, Год журнала: 2024, Номер unknown, С. 1 - 15

Опубликована: Июнь 25, 2024

Angiogenesis is considered a hallmark pathophysiological process in tumor development. Aberrant vasculature resulting from angiogenesis plays critical role the development of resistance to breast cancer treatments,

Язык: Английский

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Rhenium(I) coordinated carbon nitride as type II immunogenic cell death inducers for enhancing photoimmunotherapy against triple-negative breast cancer

Chemical Engineering Journal, Год журнала: 2024, Номер 485, С. 150154 - 150154

Опубликована: Март 2, 2024

Язык: Английский

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IMpassion132 double-blind randomised phase III trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer

Annals of Oncology, Год журнала: 2024, Номер 35(7), С. 630 - 642

Опубликована: Май 15, 2024

•Data on outcomes in patients with rapidly relapsing TNBC are scarce.•The phase III IMpassion132 trial enrolled relapse <12 months after chemotherapy/surgery for early TNBC.•OS was not improved by adding atezolizumab to chemotherapy PD-L1-positive TNBC.•Patients have a dismal prognosis and represent population huge unmet need. BackgroundImmune checkpoint inhibitors improve the efficacy of first-line programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data aTNBC scarce.Patients methodsIMpassion132 (NCT03371017) last dose (anthracycline taxane required) or surgery TNBC. PD-L1 status centrally assessed using SP142 before randomisation. Initially were irrespective status. From August 2019, enrolment restricted (tumour immune cell ≥1%) aTNBC. Patients 1:1 placebo 1200 mg every 21 days investigator-selected until disease progression unacceptable toxicity. Stratification factors regimen (carboplatin plus gemcitabine capecitabine monotherapy), visceral (lung and/or liver) metastases (initially) The primary endpoint overall survival (OS), tested hierarchically tumours then, if positive, modified intent-to-treat (mITT) (all-comer pre-August 2019). Secondary endpoints included progression-free (PFS), objective response rate (ORR) safety.ResultsAmong 354 aTNBC, 68% had disease-free interval <6 73% received carboplatin/gemcitabine. OS hazard ratio 0.93 (95% confidence 0.73-1.20, P = 0.59; median 11.2 versus 12.1 atezolizumab). mITT subgroup results consistent. Median PFS 4 across treatment arms populations. ORRs 28% 40% atezolizumab. Adverse events (predominantly haematological) similar between as expected carboplatin/gemcitabine following recent exposure.ConclusionsOS, which is within months, chemotherapy. A biology-based definition intrinsic resistance immunotherapy urgently needed develop novel therapies these next-generation clinical trials. Immune scarce. safety. Among exposure. OS,

Язык: Английский

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Breaking Barriers: The Promise and Challenges of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer

Biomedicines, Год журнала: 2024, Номер 12(2), С. 369 - 369

Опубликована: Фев. 5, 2024

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with pronounced immunogenicity, exhibiting rapid proliferation and immune cell infiltration into the tumor microenvironment. TNBC’s heterogeneity poses challenges to immunological treatments, inducing resistance mechanisms in Therapeutic modalities, including checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, CTLA-4, are explored preclinical clinical trials. Promising results emerge from combining ICIs anti-TGF-β VISTA, hindering TNBC growth. cells employ complex evasion strategies involving interactions stromal cells, suppressing recognition through various cytokines, chemokines, metabolites. The recent focus on unraveling humoral cellular components aims disrupt crosstalk within This review identifies latest mechanisms, exploring potential targets for trials overcome enhance patient survival rates.

Язык: Английский

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Sciatic nerve stimulation enhances NK cell cytotoxicity through dopamine signaling and synergizes immunotherapy in triple-negative breast cancer

Drug Resistance Updates, Год журнала: 2025, Номер 79, С. 101212 - 101212

Опубликована: Фев. 10, 2025

Язык: Английский

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Bisphenol A and DDT disrupt adipocyte function in the mammary gland: implications for breast cancer risk and progression

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Фев. 17, 2025

As breast cancer incidence continues to rise worldwide, there is a pressing need understand the environmental factors that contribute its development. Obesogens, including Bisphenol A (BPA) and Dichlorodiphenyltrichloroethane (DDT), are highly prevalent in environment, have been associated with obesity metabolic dysregulation. BPA DDT, known disrupt hormone signaling epithelial cells, also promote adipogenesis, lipogenesis, adipokine secretion adipose tissue, directly contributing pathogenesis of obesity. While adipose-rich mammary gland may be particularly vulnerable obesogens, scarcity research investigating obesogen-mediated changes adipocytes drive oncogenic transformation cells. Here, we review preclinical clinical evidence linking DDT impaired development risk. We discuss how obesogen-driven mechanisms obesity, secretion, could provide pro-inflammatory, nutrient-rich environment promotes activation pathways Understanding role obesogens risk progression essential for informing public health guidelines aimed at minimizing obesogen exposure, ultimately reduce improve outcomes women.

Язык: Английский

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Cell membrane coated nanoparticles as a biomimetic drug delivery platform for enhancing cancer immunotherapy

Nanoscale, Год журнала: 2024, Номер 16(18), С. 8708 - 8738

Опубликована: Янв. 1, 2024

Cancer immunotherapy, a burgeoning modality for cancer treatment, operates by activating the autoimmune system to impede growth of malignant cells. Although numerous immunotherapy strategies have been employed in clinical therapy, resistance cells immunotherapeutic medications and other apprehensions attainment sustained advantages most patients. Recent advancements nanotechnology drug delivery hold promise augmenting efficacy immunotherapy. However, is currently constrained inadequate specificity delivery, low rate response, intricate immunosuppressive tumor microenvironment. In this context, investigation cell membrane coated nanoparticles (CMNPs) has revealed their ability perform targeted immune evasion, controlled release, immunomodulation. By combining advantageous features natural membranes nanoparticles, CMNPs demonstrated unique potential realm This review aims emphasize recent research progress elucidate underlying mechanisms as an innovative platform enhancing Additionally, it provides comprehensive overview current involving different types CMNPs, with intention further exploration optimization.

Язык: Английский

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Inhibition of NLRP3 inflammasome contributes to paclitaxel efficacy in triple negative breast cancer treatment

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Окт. 21, 2024

Abstract Chronic inflammation and NLRP3 inflammasome activation are among the determining factors of breast malignancies. Paclitaxel (PTX) is a drug used in cancer treatment which sustains prolonged inflammation, reducing effectiveness chemotherapy. Considering impact inflammatory processes progression, there strong concern to develop therapeutic strategy targeting for triple-negative (TNBC) treatment. Therefore, aim this study was evaluate potential PTX modulation counterbalance TNBC by inducing programmed cell death inhibiting activity pro-inflammatory cytokines. The obtained results suggested interaction between revealed that pharmacological inhibition, using NLRP3-specific inhibitor MCC950, genetic silencing specific small interfering RNA, reduced responses facilitated PTX-determined tumor death. Thus, manipulation combination with anti-tumor drugs opens up new perspectives therapy.

Язык: Английский

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Current and future immunotherapy for breast cancer

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Дек. 25, 2024

Abstract Substantial therapeutic advancement has been made in the field of immunotherapy breast cancer. The immune checkpoint inhibitor pembrolizumab combination with chemotherapy received FDA approval for both PD-L1 positive metastatic and early-stage triple-negative cancer, while ongoing clinical trials seek to expand current treatment landscape inhibitors hormone receptor HER2 Antibody drug conjugates are approved triple negative HER2+ disease, being studied inhibitors. Vaccines bispecific antibodies areas active research. Studies cellular therapies such as tumor infiltrating lymphocytes, chimeric antigen receptor-T cells T cell engineered promising ongoing. This review provides an update recent major cancer discusses future directions

Язык: Английский

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