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Pharmaceutical Nanotechnology 2019Breast cancer therapy involves a multidisciplinary approach comprising surgery, radiotherapy, neoadjuvant and adjuvant therapy. Effective therapy of breast cancer... (Review)
Review
Breast cancer therapy involves a multidisciplinary approach comprising surgery, radiotherapy, neoadjuvant and adjuvant therapy. Effective therapy of breast cancer requires maximum therapeutic efficacy, with minimal undesirable effects to ensure a good quality of life for patients. The carefully selected combination of therapeutic interventions provides patients with the opportunity to derive maximum benefit from therapy while minimizing or eliminating recurrence, resistance and toxic effects, as well as ensuring that patients have a good quality of life. This review discusses therapeutic options for breast cancer treatments and various combinations that had been previously exploited. The review will also give an insight into the potential application of the nanotechnology platform for codelivery of therapeutics in breast cancer therapy.
Topics: Antineoplastic Agents; Breast Neoplasms; Drug Delivery Systems; Drug Resistance; Drug Therapy, Combination; Female; Humans; Molecular Targeted Therapy; Nanoparticles; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Quality of Life
PubMed: 30666921
DOI: 10.2174/2211738507666190122111224 -
Nature Communications Mar 2019Drug combinations, offering increased therapeutic efficacy and reduced toxicity, play an important role in treating multiple complex diseases. Yet, our ability to...
Drug combinations, offering increased therapeutic efficacy and reduced toxicity, play an important role in treating multiple complex diseases. Yet, our ability to identify and validate effective combinations is limited by a combinatorial explosion, driven by both the large number of drug pairs as well as dosage combinations. Here we propose a network-based methodology to identify clinically efficacious drug combinations for specific diseases. By quantifying the network-based relationship between drug targets and disease proteins in the human protein-protein interactome, we show the existence of six distinct classes of drug-drug-disease combinations. Relying on approved drug combinations for hypertension and cancer, we find that only one of the six classes correlates with therapeutic effects: if the targets of the drugs both hit disease module, but target separate neighborhoods. This finding allows us to identify and validate antihypertensive combinations, offering a generic, powerful network methodology to identify efficacious combination therapies in drug development.
Topics: Drug Combinations; Drug Development; Drug Therapy, Combination; Humans; Hypertension; Models, Biological; Protein Interaction Maps; Treatment Outcome
PubMed: 30867426
DOI: 10.1038/s41467-019-09186-x -
Annals of Oncology : Official Journal... Feb 2019Cancer immunotherapy has changed the standard of care for a subgroup of patients with advanced disease. Immune checkpoint blockade (ICB) in particular has shown improved... (Review)
Review
BACKGROUND
Cancer immunotherapy has changed the standard of care for a subgroup of patients with advanced disease. Immune checkpoint blockade (ICB) in particular has shown improved survival compared with previous standards of care for several tumor types. Although proven to be successful in more immunogenic tumors, ICB is still largely ineffective in patients with tumors that are not infiltrated by immune cells, the so-called cold tumors.
PATIENTS AND METHODS
This review describes the effects of different chemotherapeutic agents on the immune system and the potential value of these different types of chemotherapy as combination partners with ICB in patients with solid tumors. Both preclinical data and currently ongoing clinical trials were evaluated. In addition, we reviewed findings regarding different dosing schedules, including the effects of an induction phase and applying metronomic doses of chemotherapy.
RESULTS
Combining ICB with other treatment modalities may lead to improved immunological conditions in the tumor microenvironment and could thereby enhance the antitumor immune response, even in tumor types that are so far unresponsive to ICB monotherapy. Chemotherapy, that was originally thought to be solely immunosuppressive, can exert immunomodulatory effects which may be beneficial in combination with immunotherapy. Each chemotherapeutic drug impacts the tumor microenvironment differently, and in order to determine the most suitable combination partners for ICB it is crucial to understand these mechanisms.
CONCLUSION
Preclinical studies demonstrate that the majority of chemotherapeutic drugs has been shown to exert immunostimulatory effects, either by inhibiting immunosuppressive cells and/or activating effector cells, or by increasing immunogenicity and increasing T-cell infiltration. However, for certain chemotherapeutic agents timing, dose and sequence of administration of chemotherapeutic agents and ICB is important. Further studies should focus on determining the optimal drug combinations, sequence effects and optimal concentration-time profiles in representative preclinical models.
Topics: Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Cell Cycle Checkpoints; Drug Therapy, Combination; Humans; Immunotherapy; Neoplasms; Prognosis; Tumor Microenvironment
PubMed: 30608567
DOI: 10.1093/annonc/mdy551 -
Microbiology Spectrum Jan 2017Cutaneous tuberculosis (TB) may present in various clinical manifestations. Skin involvement may occur as a result of exogenous inoculation, contiguous spread from a... (Review)
Review
Cutaneous tuberculosis (TB) may present in various clinical manifestations. Skin involvement may occur as a result of exogenous inoculation, contiguous spread from a nearby focus of infection, or by hematogenous spread from a distant focus. Because the clinical presentation of cutaneous TB can vary widely, it is important to have a high index of suspicion in appropriate clinical settings. In this chapter, the various clinical manifestations of clinical TB are classified by source of infection (exogenous, endogenous, and hematogenous spread). These are linked to the clinical appearance and histology of the skin lesions. Hopefully, this will resolve the confusion created by the myriad of terms previously used in the medical literature. Once a diagnosis of cutaneous TB is entertained, a biopsy for both culture and histopathology should be submitted. In some cases histopathology may show nonspecific inflammation without classic granuloma formation. In these cases, monoclonal antibodies and polymerase chain reaction (PCR) testing may be useful. In fact, in recent years, PCR amplification has proven to be invaluable in assisting identification of M. tuberculosis from skin biopsies in patients with negative TB cultures. In most instances, treatment of cutaneous TB requires combination chemotherapy. This is especially important in patients with extra cutaneous disease, multiple skin lesions, and those with profound immunosuppression. Surgery also may play both a diagnostic and therapeutic role.
Topics: Antitubercular Agents; Bacteriological Techniques; Biopsy; Diagnostic Tests, Routine; Drug Therapy, Combination; Histocytochemistry; Humans; Immunohistochemistry; Mycobacterium tuberculosis; Polymerase Chain Reaction; Tuberculosis, Cutaneous
PubMed: 28233513
DOI: 10.1128/microbiolspec.TNMI7-0010-2016 -
Oncology Research and Treatment 2017Acquired immune deficiency syndrome (AIDS)-related lymphomas (ARL) still represent a relevant field of clinical research. For most histological subtypes of ARL, no... (Review)
Review
Acquired immune deficiency syndrome (AIDS)-related lymphomas (ARL) still represent a relevant field of clinical research. For most histological subtypes of ARL, no optimal initial therapy has been clearly defined so far. Rituximab plus chemotherapy is feasible and effective and should be offered to all patients with CD20-positive ARL regardless of their CD4 cell count. Combination antiretroviral therapy (cART) should be given concomitantly with chemotherapy, bearing in mind potential drug-drug interactions. Appropriate treatment of ARL is determined by a number of factors such as lymphoma stage, performance status, comorbidities, histological subtype, and immunosuppression. Treatment should principally be the same as in human immunodeficiency virus (HIV)-negative lymphoma patients. In HIV-related Hodgkin's lymphoma, high cure rates have been achieved with stage-adapted treatment approaches, albeit with worse outcomes compared to immunocompetent patients.
Topics: Acquired Immunodeficiency Syndrome; Anti-Retroviral Agents; Antineoplastic Agents; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Lymphoma; Medical Oncology; Practice Guidelines as Topic; Treatment Outcome
PubMed: 28253516
DOI: 10.1159/000456036 -
International Journal of Molecular... May 2023DNA topoisomerases are important enzymes that stabilize DNA supercoiling and resolve entanglements. There are two main types of topoisomerases in all cells: type I,... (Review)
Review
DNA topoisomerases are important enzymes that stabilize DNA supercoiling and resolve entanglements. There are two main types of topoisomerases in all cells: type I, which causes single-stranded DNA breaks, and type II, which cuts double-stranded DNA. Topoisomerase activity is particularly increased in rapidly dividing cells, such as cancer cells. Topoisomerase inhibitors have been an effective chemotherapeutic option for the treatment of several cancers. In addition, combination cancer therapy with topoisomerase inhibitors may increase therapeutic efficacy and decrease resistance or side effects. Topoisomerase inhibitors are currently being used worldwide, including in the United States, and clinical trials on the combination of topoisomerase inhibitors with other drugs are currently underway. The primary objective of this review was to comprehensively analyze the current clinical landscape concerning the combined application of irinotecan, an extensively investigated type I topoisomerase inhibitor for colorectal cancer, and doxorubicin, an extensively researched type II topoisomerase inhibitor for breast cancer, while presenting a novel approach for cancer therapy.
Topics: Humans; Female; Topoisomerase I Inhibitors; Breast Neoplasms; Topoisomerase II Inhibitors; Drug Therapy, Combination; Colorectal Neoplasms; DNA Topoisomerases, Type II; DNA Topoisomerases, Type I
PubMed: 37176164
DOI: 10.3390/ijms24098457 -
Trends in Cancer Nov 2022Combination chemotherapy can cure certain leukemias and lymphomas, but most solid cancers are only curable at early stages. We review quantitative principles that... (Review)
Review
Combination chemotherapy can cure certain leukemias and lymphomas, but most solid cancers are only curable at early stages. We review quantitative principles that explain the benefits of combining independently active cancer therapies in both settings. Understanding the mechanistic principles underlying curative treatments, including those developed many decades ago, is valuable for improving future combination therapies. We discuss contemporary evidence for long-established but currently neglected ideas of how combination therapy overcomes tumor heterogeneity. We show that a unified model of interpatient and intratumor heterogeneity describes historical progress in the treatment of pediatric acute lymphocytic leukemia (ALL), in which increasingly intensive combination regimens ultimately achieved high cure rates. We also describe three distinct aspects of drug independence that apply at different biological scales. The ability of these principles to quantitatively explain curative regimens suggests that supra-additive (synergistic) drug interactions are not required for successful combination therapy.
Topics: Child; Humans; Antineoplastic Combined Chemotherapy Protocols; Neoplasms; Lymphoma; Combined Modality Therapy; Leukemia
PubMed: 35842290
DOI: 10.1016/j.trecan.2022.06.009 -
International Journal of Molecular... Aug 2020Hematological malignancies define a highly heterogeneous set of blood-, bone marrow-, and organ-associated diseases with highly variable prognoses that constantly...
Hematological malignancies define a highly heterogeneous set of blood-, bone marrow-, and organ-associated diseases with highly variable prognoses that constantly relapse upon treatment [...].
Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Resistance, Neoplasm; Drug Therapy, Combination; Hematologic Neoplasms; Humans; Immunotherapy; Immunotherapy, Adoptive; Molecular Targeted Therapy
PubMed: 32847013
DOI: 10.3390/ijms21176091 -
BMJ Clinical Evidence Sep 2010Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic... (Review)
Review
INTRODUCTION
Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered unusual.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line hormonal treatment? What are the effects of second-line hormonal treatment in women who have not responded to tamoxifen? What are the effects of first-line chemotherapy? What are the effects of first-line chemotherapy in combination with a monoclonal antibody? What are the effects of second-line chemotherapy? What are the effects of treatments for bone metastases? What are the effects of treatments for spinal cord metastases? What are the effects of treatments for cerebral or choroidal metastases? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 77 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: first-line hormonal treatment using anti-oestrogens (tamoxifen), ovarian ablation, progestins, selective aromatase inhibitors, or combined gonadorelin analogues plus tamoxifen; second-line hormonal treatment using progestins or selective aromatase inhibitors; first-line non-taxane combination chemotherapy; first-line taxane-based combination chemotherapy; first-line high- versus low-dose standard chemotherapy; first-line chemotherapy plus monoclonal antibody (bevacizumab, trastuzumab); first-line chemotherapy plus tyrosine kinase inhibitor (lapatinib); second-line taxane-based combination chemotherapy; second-line capecitabine or semi-synthetic vinca alkaloids for anthracycline-resistant disease; second-line chemotherapy plus tyrosine kinase inhibitor (lapatinib); and treatment for bone, spinal, or choroidal metastases using bisphosphonates, intrathecal chemotherapy, radiotherapy (alone or plus corticosteroids) radiation sensitisers, or surgical resection.
Topics: Administration, Oral; Breast Neoplasms; Drug Therapy, Combination; Humans; Protein Kinase Inhibitors
PubMed: 21418674
DOI: No ID Found -
European Review For Medical and... Feb 2021Over-expression of COX-2 has been linked with various molecular signaling such as carcinogenesis, invasiveness, and malignant tumour metastasis. Besides, the use of...
OBJECTIVE
Over-expression of COX-2 has been linked with various molecular signaling such as carcinogenesis, invasiveness, and malignant tumour metastasis. Besides, the use of celecoxib is also related to lowering the risk of breast cancer. This study therefore designed to explore the synergistic inhibitory effect of the combination of curcumin and celecoxib on the growth of human breast cancer cells.
MATERIALS AND METHODS
In our investigation, we treated MDA-MB-231 cancer cells with different concentrations of curcumin and celecoxib. The enzyme-linked immunoassay was used to measure the COX-2 expression levels. MDA-MB-231 growth was examined by MTS cell viability assay, and synergy detection was carried out using combination index approaches. The drug-likeliness of the tested drugs (curcumin and celecoxib) were computed and predicted ADME pharmacokinetic parameters by in silico. Further, we have conducted BOILED-Egg plot and bioavailability radar analysis for the curcumin and celecoxib.
RESULTS
The result of the physicochemical and ADMET/pharmacokinetic properties showed that these two drugs have good oral and optically bioavailable absorption. The present in silico study could offer a reliable theoretical basis for future structural modification of these compounds to treat breast cancer. The in vitro results suggested that curcumin and celecoxib individually inhibited the growth of MDA-MB-231 cells in a dose-dependent manner. The effect was synergistic for MDA-MB-231 cells relative to the two compounds individually. The synergistic growth inhibitory effect was mediated by a mechanism that possibly involves inhibition of the COX-2 pathways.
CONCLUSIONS
Our findings show the prominent anti-proliferative effects of celecoxib and/or curcumin on MDA-MB-231 cells, providing a rationale for further detailed preclinical and potential clinical studies of this combination for breast cancer therapy. Further, these computed parameters suggested that curcumin possesses a high tendency to act as an adjuvant drug with celecoxib in the treatment of breast cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Celecoxib; Cell Proliferation; Cell Survival; Curcumin; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Drug Screening Assays, Antitumor; Drug Therapy, Combination; Female; Humans; Tumor Cells, Cultured
PubMed: 33660801
DOI: 10.26355/eurrev_202102_25086