Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: July 6, 2023

Abstract Breast cancer is the second leading cause of death for women worldwide. The heterogeneity this disease presents a big challenge in its therapeutic management. However, recent advances molecular biology and immunology enable to develop highly targeted therapies many forms breast cancer. primary objective therapy inhibit specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, different growth factors have emerged as potential targets subtypes. Many drugs are currently undergoing clinical trials, some already received FDA approval monotherapy or combination with other treatment yet achieve promise against triple-negative (TNBC). In aspect, immune has come up promising approach specifically TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, adoptive cell transfer been extensively studied setting cancer, especially approved blockers chemotherapeutic treat several trials ongoing. This review provides an overview developments advancements immunotherapies treatment. successes, challenges, prospects were critically discussed portray their profound prospects.

Language: Английский

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Targeting Breast Cancer: An Overlook on Current Strategies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3643 - 3643

Published: Feb. 11, 2023

Breast cancer (BC) is one of the most widely diagnosed cancers and a leading cause death among women worldwide. Globally, BC second frequent first gynecological one, affecting with relatively low case-mortality rate. Surgery, radiotherapy, chemotherapy are main treatments for BC, even though latter often not aways successful because common side effects damage caused to healthy tissues organs. Aggressive metastatic BCs difficult treat, thus new studies needed in order find therapies strategies managing these diseases. In this review, we intend give an overview field, presenting data from literature concerning classification drugs used therapy treatment BCs, along clinical studies.

Language: Английский

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Prolactin receptor signaling: A novel target for cancer treatment - Exploring anti-PRLR signaling strategies

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 13, 2023

Prolactin (PRL) is a peptide hormone mainly secreted from the anterior pituitary gland. PRL reported to play role in pregnancy, mammary gland development, immune modulation, reproduction, and differentiation of islet cells. binds its receptor PRLR, which belongs superfamily class I cytokine that has no intrinsic kinase activity. In canonical signaling, binding PRLR induces downstream signaling including JAK-STAT, AKT MAPK pathways. This leads increased cell proliferation, stemness, migration, apoptosis inhibition, resistance chemotherapy. PRL-signaling upregulated numerous hormone-dependent cancers breast, prostate, ovarian, endometrial cancer. However, more recently, pathway been tumor-promoting other cancer types such as colon, pancreas, hepatocellular cancers. Hence, an attractive target for drug development with blockade being potential therapeutic approach. Different strategies have developed this modification peptides (Del1-9-G129R-hPRL, G129R-Prl), growth receptor/prolactin bispecific antibody antagonist, neutralizing LFA102, antibody-drug conjugate (ABBV-176) humanized h16f (PR-1594804) pyrrolobenzodiazepine dimer, targeting both CD3, vivo half-life extended fusion protein containing antagonist PrlRA albumin domain. There also attempts discover develop small molecular inhibitors PRLR. Recently, using structure-based virtual screening, we identified few antipsychotic drugs penfluridol molecule inhibits inhibit PDAC tumor progression. review, will summarize recent advances biology give account treatment

Language: Английский

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HER2/PI3K/AKT pathway in HER2-positive breast cancer: A review

Medicine, Journal Year: 2024, Volume and Issue: 103(24), P. e38508 - e38508

Published: June 14, 2024

Breast cancer is currently the most commonly occurring globally. Among breast cases, human epidermal growth factor receptor 2 (HER2)-positive accounts for 15% to 20% and a crucial focus in treatment of cancer. Common HER2-targeted drugs approved treating early and/or advanced include trastuzumab pertuzumab, which effectively improve patient prognosis. However, despite treatment, patients with terminal HER2-positive ultimately suffer death from disease due primary or acquired drug resistance. The prevalence aberrantly activated protein kinase B (AKT) signaling was already observed previous studies. It well known that p-AKT expression linked an unfavorable prognosis, phosphatidylinositol-3-kinase (PI3K)/AKT pathway, as common mutated pathway cancer, plays major role mechanism Therefore, current review, we summarize molecular alterations present elucidate relationships between HER2 overexpression PI3K/AKT pathways resistant targeting HER2-AKT will provide adjunctive therapeutic rationale subsequent resistance directed therapy future.

Language: Английский

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Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(1), P. 209 - 209

Published: Jan. 16, 2022

The dysregulation of gene expression is a critical event involved in all steps tumorigenesis. Aberrant histone and non-histone acetylation modifications due to the abnormal activation deacetylases (HDAC) have been reported hematologic solid types cancer. In this sense, cancer-associated epigenetic alterations are promising targets for anticancer therapy chemoprevention. HDAC inhibitors (HDACi) induce hyperacetylation within target proteins, altering cell cycle proliferation, differentiation, regulation death programs. Over last three decades, an increasing number synthetic naturally derived compounds, such as dietary-derived products, demonstrated act HDACi provided biological molecular insights with regard role first part review focused on roles Zinc-dependent family malignant diseases. Accordingly, small-molecules natural products described terms cancer Furthermore, structural considerations included improve selectivity combinatory potential other specific targeting agents bifunctional proteolysis chimeras. Additionally, clinical trials that combine current therapies discussed, which may open new avenues feasibility HDACi’s future applications precision therapies.

Language: Английский

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The role of transketolase in human cancer progression and therapy

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 154, P. 113607 - 113607

Published: Aug. 26, 2022

Transketolase (TKT) is an enzyme that ubiquitously expressed in all living organisms and has been identified as important regulator of cancer. Recent studies have shown the TKT family includes gene two TKT-like (TKTL) genes; TKTL1 TKTL2. reported to be involved regulation multiple cancer-related events, such cancer cell proliferation, metastasis, invasion, epithelial-mesenchymal transition, chemoradiotherapy resistance, patient survival prognosis. Therefore, may ideal target for treatment. More importantly, levels were detected using EDIM technology early detection some malignancies, was more sensitive specific than traditional tumor markers. Detecting before after surgery could used evaluate surgery's effect. While targeted suppresses ways, cases, it detrimental effects on organism. In this review, we discuss role different tumors detailed mechanisms while evaluating its value limitations clinical applications. review provides a basis application therapy future, strategy subsequent research.

Language: Английский

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The immunotoxin targeting PRLR increases tamoxifen sensitivity and enhances the efficacy of chemotherapy in breast cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: June 20, 2024

Abstract Background Though tamoxifen achieves success in treating estrogen receptor α (ERα)-positive breast cancer, the followed development of resistance is a common challenge clinic. Signals downstream prolactin (PRLR) could synergize with ERα cancer progression. However, potential effect targeting PRL-PRLR axis combined has not been thoroughly investigated. Methods High-throughput RNA-seq data obtained from TCGA, Metabric and GEO datasets were analyzed to explore PRLR expression cell association treatment. Exogenous or PRL overexpression models employed investigate role activated pathway mediating insensitivity. Immunotoxin (N8-PE24) was constructed splicing-intein technique, efficacy N8-PE24 against evaluated using vitro vivo methods, including analysis cells growth apoptosis, 3D spheroids culture, animal xenografts. Results by significantly decrease sensitivity ERα-positive tamoxifen. Tamoxifen treatment upregulated transcription induce significant accumulation protein alkalizing lysosomes. Meanwhile, tamoxifen-resistant MCF7 achieved long-term pressure exhibited both level PRLR. enhanced vivo. In xenograft models, paclitaxel when PRLR-positive triple-negative cancer. Conclusions potentially associates insensitivity cells. inhibit cancers promote drug paclitaxel. Our study provides new perspective for treat

Language: Английский

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Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer

Cancers, Journal Year: 2022, Volume and Issue: 14(14), P. 3305 - 3305

Published: July 6, 2022

Despite the improvement achieved by introduction of HER2-targeted therapy, up to 25% early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse. Beyond trastuzumab, other agents approved for HER2+ BC include monoclonal antibody pertuzumab, antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine have also shown a significant metastatic setting. Other therapeutic strategies overcome treatment resistance been explored BC, mainly that overexpress estrogen receptors (ER+). In ER+ patients, target therapies phosphoinositide-3-kinase (PI3K) pathway inhibition cyclin-dependent kinases 4/6 blocking may be effective controlling downstream many cellular pathways associated therapies. Multiple trials these some promising results, probably, next years conclusive results succeed. addition, is known more immunogenic than subgroups, high variability between tumors. Different immunotherapeutic HER-2 therapy plus checkpoint inhibitors, new vaccines approaches investigated this setting, but controversial obtained date.

Language: Английский

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Breast Cancer and Prolactin – New Mechanisms and Models

Endocrinology, Journal Year: 2022, Volume and Issue: 163(10)

Published: Aug. 4, 2022

Abstract The pathogenesis of breast cancer is driven by multiple hormones and growth factors. One these, prolactin (PRL), contributes to both mammary differentiation oncogenesis, yet the basis for these disparate effects has remained unclear. focus this review examine place into context 2 recent studies that have provided insight roles PRL receptors in tumorigenesis tumor progression. study provides novel evidence opposing actions being mediated part differential receptor (PRLr) isoform utilization. Briefly, homomeric complexes long PRLr (PRLrL-PRLrL) promotes differentiation, while heteromeric intermediate (PRLrI-PRLrL) isoforms trigger oncogenesis. Another describes an immunodeficient, prolactin-humanized mouse model, NSG-Pro, facilitates receptor-expressing patient-derived xenografts. Evidence obtained with model supports interactions physiological levels estrogen ERBB2 gene networks, modulatory on drug responsiveness, pro-metastatic cancer. This progress concepts, mechanisms experimental models expected renew interest harnessing/exploiting signaling therapeutic

Language: Английский

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PRL-mediated STAT5B/ARRB2 pathway promotes the progression of prostate cancer through the activation of MAPK signaling

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(2)

Published: Feb. 10, 2024

Abstract Previous study showed that higher expression of prolactin (PRL) was found in CRPC samples compared with hormone-naive prostate cancer (HNPC) and benign prostatic hyperplasia (BPH) samples. We further investigate the function PRL (PCa) explored its downstream effects. heterogeneous PRLR clinical The VCaP 22Rv1 cells exhibited expression. Among proteins, STAT5B dominant subtype cell lines. Human recombinant stimulation PCa resulted increased phosphorylation STAT5B(pSTAT5B) progression vitro vivo, knockdown can suppress malignant behavior PCa. To understand mechanism further, we performed Bioinformatic analysis, ChIP qPCR, luciferase reporter gene assay. results revealed ARRB2 transcription target STAT5B, related to aggression poorer prognosis Additionally, Gene set enrichment analysis indicated significantly enriched MAPK signaling pathway. Immunohistochemistry (IHC) demonstrated elevated pSTAT5B, ARRB2, pERK1/2 levels tissues HNPC BPH. Mechanically, enhanced activation pathway by binding ERK1/2, thereby promoting ERK1/2 (pERK1/2). In conclusion, our promote through STAT5B/ARRB2 signaling, which be suppressed intervention targeting STAT5B. Blockade a potential therapeutic for

Language: Английский

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