Recent advances in targeted strategies for triple-negative breast cancer

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 28, 2023

Triple-negative breast cancer (TNBC), a highly aggressive subtype of cancer, negatively expresses estrogen receptor, progesterone and the human epidermal growth factor receptor 2 (HER2). Although chemotherapy is main form treatment for patients with TNBC, effectiveness TNBC still limited. The search more effective therapies urgent. Multiple targeted therapeutic strategies have emerged according to specific molecules signaling pathways expressed in TNBC. These include PI3K/AKT/mTOR inhibitors, Notch poly ADP-ribose polymerase antibody-drug conjugates. Moreover, immune checkpoint example, pembrolizumab, atezolizumab, durvalumab, are widely explored clinic. We summarize recent advances therapy immunotherapy aim serving as reference development individualized future.

Language: Английский

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Parps in immune response: Potential targets for cancer immunotherapy

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: 234, P. 116803 - 116803

Published: Feb. 16, 2025

Language: Английский

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Mechanism of PARP inhibitor resistance and potential overcoming strategies

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(1), P. 306 - 320

Published: March 24, 2023

PARP inhibitors (PARPi) are a kind of cancer therapy that targets poly (ADP-ribose) polymerase. PARPi is the first clinically approved drug to exert synthetic lethality by obstructing DNA single-strand break repair process. Despite significant therapeutic effect in patients with homologous recombination (HR) deficiency, innate and acquired resistance main challenge clinic. In this review, we mainly discussed underlying mechanisms summarized promising solutions overcome resistance, aiming at extending application improving patient outcomes.

Language: Английский

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Recent Therapeutic Advances in Gynecologic Oncology: A Review

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 770 - 770

Published: Feb. 13, 2024

Gynecologic malignancies have high incidence rates both nationally and internationally, cervical, endometrial, ovarian cancers account for mortality worldwide. Significant research is ongoing to develop targeted therapies address unmet needs in the field improve patient outcomes. As tumors mutate progress through traditional lines of treatment, new must be developed overcome resistance target cancer-specific receptors mutations. Recent advances development immunotherapy antibody–drug conjugates resulted compelling clinically meaningful results cancers. In last decade, several agents received FDA approval or NCCN guideline recommendation treatment gynecologic malignancies, including dostarlimab advanced recurrent endometrial cancer pembrolizumab cervical Several other immunotherapeutic are under active investigation. Development tisotumab vedotin cancer, mirvetuximab soravtansine trastuzumab deruxtecan multiple has translated into exciting efficacy signals, prompting full drug approvals additional This article aims review recent novel treatments highlighting trials data underlying these interventions.

Language: Английский

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Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 176, P. 116909 - 116909

Published: June 8, 2024

Lung cancer is a prevalent malignant tumor and leading cause of cancer-related fatalities globally. However, current treatments all have limitations. Therefore, there an urgent need to identify readily available therapeutic agent counteract lung development progression. Luteolin flavonoid derived from vegetables herbs that possesses preventive effects on various cancers. With the goal providing new directions for treatment cancer, we review here recent findings luteolin so as provide ideas anti-lung drugs. The search focused studies published between January 1995 2024 explored use in cancer. A comprehensive literature was conducted SCOPUS, Google Scholar, PubMed, Web Science databases using keywords "luteolin" "lung cancer." By collecting previous literature, found has multiple mechanisms effects, including promotion apoptosis cells; inhibition cell proliferation, invasion metastasis; modulation immune responses. In addition, it can be used adjuvant radio-chemotherapy helps ameliorate complications. This summarizes structure, natural sources, physicochemical properties pharmacokinetics luteolin, focuses mechanism

Language: Английский

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MAPK Signaling‐Mediated RFNG Phosphorylation and Nuclear Translocation Restrain Oxaliplatin‐Induced Apoptosis and Ferroptosis

Advanced Science, Journal Year: 2024, Volume and Issue: 11(38)

Published: Aug. 9, 2024

Chemotherapy resistance remains a major challenge in the treatment of colorectal cancer (CRC). Therefore, it is crucial to develop novel strategies sensitize cells chemotherapy. Here, fringe family screened determine their contribution chemotherapy CRC. It found that RFNG depletion significantly sensitizes oxaliplatin treatment. Mechanistically, chemotherapy-activated MAPK signaling induces ERK phosphorylate Ser255 residue. Phosphorylated S255 (pS255) interacts with nuclear importin proteins KPNA1/importin-α1 and KPNB1/importin-β1, leading its translocation into nucleus where targets p53 inhibits phosphorylation by competitively inhibiting binding CHK2 p53. Consequently, expression CDKN1A decreased SLC7A11 increased, inhibition apoptosis ferroptosis. In contrast, phosphor-deficient S225A mutant showed increased ferroptosis, exhibited notable response both vitro vivo. further revealed patients low pS255 significant sensitivity patient-derived xenograft (PDX) model. These findings highlight crosstalk between pathways through RFNG, which mediates Additionally, this study provides guidance for CRC patients.

Language: Английский

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Comprehensive multi-omics analyses exposes a precision therapy strategy that targets replication stress in hepatocellular carcinoma using WEE1 inhibition

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Evaluating the efficacy of PARP inhibitor in ARID1A-deficient colorectal cancer: A ex vivo study

Cancer Biomarkers, Journal Year: 2025, Volume and Issue: 42(3)

Published: March 1, 2025

ARID1A mutations are a common occurrence in colorectal cancer (CRC) cells, but clinical therapeutic options targeting this anomaly remain unavailable. The loss of functionality compromises DNA damage repair processes, potentially causing cells to rely more heavily on PARP-dependent pathways preserve genomic integrity, thereby making them susceptible PARP inhibitor (PARPi) therapy. To evaluate the suitability PARPi treatment for CRC patients with sufficiency (ARID1A+) and deficiency (ARID1A-), our study enrolled 80 who had undergone surgical primary CRC. Surgical specimens underwent immunohistochemical examination assess protein expression. explored correlations between expression clinicopathological characteristics. Moreover, were isolated through enzymatic digestion validated using carcinoma marker CK20. Subsequently, sensitivity was investigated untreated ARID1A+ ARID1A- an ATP-tumor chemosensitivity assay (ATP-TCA). Additionally, we confirmed efficacy these clone formation assessed its impact cell cycle dynamics, apoptosis, signaling immunofluorescence flow cytometry. results demonstrated that group displayed greater compared group. led increased tumor death Mechanistically, resulted abnormalities, particularly G2/M phase arrest, which further exacerbated by treatment. Furthermore, significantly number RAD51 foci lines. In conclusion, highlights potential as effective option patients.

Language: Английский

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Perspectives and mechanisms for targeting mitotic catastrophe in cancer treatment

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(5), P. 188965 - 188965

Published: Aug. 23, 2023

Language: Английский

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Combination of PARP inhibitor and CDK4/6 inhibitor modulates cGAS/STING‐dependent therapy‐induced senescence and provides “one‐two punch” opportunity with anti‐PD‐L1 therapy in colorectal cancer

Cancer Science, Journal Year: 2023, Volume and Issue: 114(11), P. 4184 - 4201

Published: Sept. 13, 2023

Although PARP inhibitor (PARPi) has been proven to be a promising anticancer drug in cancer patients harboring BRCA1/2 mutation, it provides limited clinical benefit colorectal with low prevalence of mutations. In our study, we found PARPi talazoparib significantly induced cellular senescence via inhibiting p53 ubiquitination and activating p21. Furthermore, CDK4/6i palbociclib amplified this therapy-induced (TIS) vitro vivo. Mechanistically, combination senescence-associated secretory phenotype (SASP), characterization SASP components revealed type I interferon (IFN)-related mediators, which were by cGAS/STING signaling. More importantly, RNA sequencing data indicated that therapy activated T cell signatures treatment transformed the tumor microenvironment (TME) into more antitumor state increased CD8 cells natural killer (NK) decreased macrophages granulocytic myeloid-derived suppressor (G-MDSCs). Moreover, clearance TIS αPD-L1 promoted survival immunocompetent mouse models. Collectively, elucidated synergistic immunomodulatory mechanisms talazoparib-palbociclib combination. Further PD-L1 antibody might "one-two punch" therapeutic strategy for patients.

Language: Английский

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