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Journal articles on the topic 'Combination drug therapies'

Author: Grafiati

Published: 10 December 2022

Last updated: 31 July 2025

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1

Hoeller, Christoph. "The future of combination therapies in advanced melanoma." memo - Magazine of European Medical Oncology 13, no. 3 (2020): 309–13. http://dx.doi.org/10.1007/s12254-020-00640-x.

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Summary The combination of Cytotoxic T-Lymphozyte Antigen-4 (CTLA‑4) and Programmed death-1 (PD‑1) antibodies and the combination of BRAF and MEK inhibitors are the current clinical standards for combination immune and targeted therapy for melanoma, respectively. The success of these therapies has stimulated research into novel drug combinations for melanoma, of which a large majority are based on combination with PD‑1 or PD-Ligand 1 (PD-L1) blocking drugs. Thus, the aim is to provide an overview of the most important combination strategies in late stage clinical development and an outlook on

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Rideout, Todd C., Scott V. Harding, Christopher P. F. Marinangeli, and Peter J. H. Jones. "Combination drug–diet therapies for dyslipidemia." Translational Research 155, no. 5 (2010): 220–27. http://dx.doi.org/10.1016/j.trsl.2009.12.005.

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Blumer, Vanessa, and Muthiah Vaduganathan. "A rationale for dedicated trials of combination therapy in heart failure." European Heart Journal Supplements 24, Supplement_L (2022): L49—L52. http://dx.doi.org/10.1093/eurheartjsupp/suac116.

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Abstract As heart failure (HF) enters a new era with high level of evidence supporting the use of individual drug therapies, we put forth a rationale for the need for dedicated investigation of the safety, tolerability, and practicalities associated with combination medical therapy. Being able to tailor therapies via combination approaches might offer a way to maximize benefits of available therapies and also facilitate compliance. The evidentiary bar to support multi-drug regimens should be raised in HF for a variety of reasons: (1) Pivotal HF randomized controlled trials (RCTs) to date have

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Plana, Deborah, Adam C. Palmer, and Peter K. Sorger. "Independent Drug Action in Combination Therapy: Implications for Precision Oncology." Cancer Discovery 12, no. 3 (2022): 606–24. http://dx.doi.org/10.1158/2159-8290.cd-21-0212.

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Abstract Combination therapies are superior to monotherapy for many cancers. This advantage was historically ascribed to the ability of combinations to address tumor heterogeneity, but synergistic interaction is now a common explanation as well as a design criterion for new combinations. We review evidence that independent drug action, described in 1961, explains the efficacy of many practice-changing combination therapies: it provides populations of patients with heterogeneous drug sensitivities multiple chances of benefit from at least one drug. Understanding response heterogeneity could rev

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Gilad, Yosi, Gary Gellerman, David M. Lonard, and Bert W. O’Malley. "Drug Combination in Cancer Treatment—From Cocktails to Conjugated Combinations." Cancers 13, no. 4 (2021): 669. http://dx.doi.org/10.3390/cancers13040669.

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It is well recognized today that anticancer drugs often are most effective when used in combination. However, the establishment of chemotherapy as key modality in clinical oncology began with sporadic discoveries of chemicals that showed antiproliferative properties and which as a first attempt were used as single agents. In this review we describe the development of chemotherapy from its origins as a single drug treatment with cytotoxic agents to polydrug therapy that includes targeted drugs. We discuss the limitations of the first chemotherapeutic drugs as a motivation for the establishment

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Rai, Manoj P., Akshit Chitkara, Rajat Thawani, and Emerson Yu-sheng Chen. "Trends in FDA approval of solid tumor therapies with analysis of single-agent vs. combination therapies." Journal of Clinical Oncology 41, no. 16_suppl (2023): e13659-e13659. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e13659.

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e13659 Background: Single agents replacing previous therapies are ideal, but combination therapies with two or more active agents have been proposed to decrease drug resistance, promote mechanistic synergy, and/or have additive cytotoxic effects in cancer treatment. However, approval of combination therapies may increase exposure to new and former drugs, leading to more costs and time commitments to patients. Methods: This retrospective analysis examines all FDA-approved drugs for malignant solid tumors from January 2011 to December 2022. We used the data presented in the package inserts on th

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Hwangbo, Haeun, and Adam C. Palmer. "Abstract 2739: Defining and evaluating drug additivity in clinical trials of combination cancer therapy." Cancer Research 82, no. 12_Supplement (2022): 2739. http://dx.doi.org/10.1158/1538-7445.am2022-2739.

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Abstract BACKGROUND The benefits of combination therapy are often attributed to synergy, that is, drug interactions resulting in an anti-cancer effect that is more than the sum of its parts. Accordingly, the rationale for designing new drug combinations is often based on synergy measured in preclinical models. However, preclinical metrics of drug interaction are not applicable to clinical trial data, and there has been no established quantitative method to assess synergy versus additivity in clinical settings. We recently showed that because of extensive patient-to-patient heterogeneity in sin

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Azam, Faruque, and Alexei Vazquez. "Trends in Phase II Trials for Cancer Therapies." Cancers 13, no. 2 (2021): 178. http://dx.doi.org/10.3390/cancers13020178.

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Background: Drug combinations are the standard of care in cancer treatment. Identifying effective cancer drug combinations has become more challenging because of the increasing number of drugs. However, a substantial number of cancer drugs stumble at Phase III clinical trials despite exhibiting favourable efficacy in the earlier Phase. Methods: We analysed recent Phase II cancer trials comprising 2165 response rates to uncover trends in cancer therapies and used a null model of non-interacting agents to infer synergistic and antagonistic drug combinations. We compared our latest efficacy datas

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Mason-Osann, Emily, Amy E. Pomeroy, Adam C. Palmer, and Jerome T. Mettetal. "Abstract 3456: Synergistic drug combinations promote the development of resistance in acute myeloid leukemia." Cancer Research 83, no. 7_Supplement (2023): 3456. http://dx.doi.org/10.1158/1538-7445.am2023-3456.

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Abstract Background: Combination therapies are frequently employed as part of cancer treatment, often with the goal of preventing or slowing the development of drug resistance. Empirically developed combination therapies have had remarkable impact on cancer survival, yet the task of using preclinical data to predict combinations that will yield clinical benefits remains a challenge. Current combination strategies often prioritize drug synergy, where short-term effect of a drug combination is more than additive. However, prior studies of antibiotic resistance have shown that synergistic combina

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Webster, Rachel M. "Combination therapies in oncology." Nature Reviews Drug Discovery 15, no. 2 (2016): 81–82. http://dx.doi.org/10.1038/nrd.2016.3.

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Pettus, Kevin, Samera Sharpe, and John R. Papp. "In VitroAssessment of Dual Drug Combinations To Inhibit Growth of Neisseria gonorrhoeae." Antimicrobial Agents and Chemotherapy 59, no. 4 (2015): 2443–45. http://dx.doi.org/10.1128/aac.04127-14.

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ABSTRACTThe development of resistance to first-line antimicrobial therapies has led to recommendations for combination therapies for the treatment of gonorrhea infection. Recent studies have shown the success of combination therapies in treating patients, but few have reported on thein vitroactivities of these drug combinations. Anin vitroassessment of azithromycin in combination with gentamicin demonstrated inhibition of growth and suggests that clinical trials may be warranted to assess the utility of this combination in treating gonorrhea infections.

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Almutairi, Nawal Hlal, Nawal Ganai M. Bahari, Alhanouf Zaid Almutairi, et al. "Combination therapies: Innovative strategies for enhancing treatment outcomes." International journal of health sciences 7, S1 (2023): 3329–40. http://dx.doi.org/10.53730/ijhs.v7ns1.15028.

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Background: Tuberculosis (TB) is a significant global health issue requiring prolonged treatment regimens that often involve multiple medications. Mycobacterium tuberculosis, the causative agent, is capable of residing in various tissue compartments during infection, leading to variability in drug accessibility and susceptibility. The complexity of the infection necessitates the use of antibiotic combinations to ensure that all affected areas are effectively treated. Despite the importance of these combinations, their design has traditionally been addressed relatively late in the drug developm

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Korkut, Anil, Xubin Li, Elizabeth Kong, et al. "Abstract LB119: Precision combination therapies based on recurrent oncogenic co-alterations." Cancer Research 82, no. 12_Supplement (2022): LB119. http://dx.doi.org/10.1158/1538-7445.am2022-lb119.

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Abstract Cancer cells depend on multiple driver alterations whose oncogenic effects can be suppressed by drug combinations. Discovering effective combination therapies and selecting patients to maximize therapeutic benefit are challenging due to the complexity of the molecular landscape of drug responses. Here, we provide a comprehensive resource of precision combination therapies tailored to oncogenic co-alterations that are recurrent across patient cohorts. To generate the resource, we developed REcurrent Features Leveraged for Combination Therapy (REFLECT), which integrates machine learning

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Leary, Meghan, Sarah Heerboth, Karolina Lapinska, and Sibaji Sarkar. "Sensitization of Drug Resistant Cancer Cells: A Matter of Combination Therapy." Cancers 10, no. 12 (2018): 483. http://dx.doi.org/10.3390/cancers10120483.

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Cancer drug resistance is an enormous problem. It is responsible for most relapses in cancer patients following apparent remission after successful therapy. Understanding cancer relapse requires an understanding of the processes underlying cancer drug resistance. This article discusses the causes of cancer drug resistance, the current combination therapies, and the problems with the combination therapies. The rational design of combination therapy is warranted to improve the efficacy. These processes must be addressed by finding ways to sensitize the drug-resistant cancers cells to chemotherap

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Yordanova, Anna, and Hojjat Ahmadzadehfar. "Combination Therapies with PRRT." Pharmaceuticals 14, no. 10 (2021): 1005. http://dx.doi.org/10.3390/ph14101005.

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Peptide receptor radionuclide therapy (PRRT) is a successful targeted radionuclide therapy in neuroendocrine tumors (NETs). However, complete responses remain elusive. Combined treatments anticipate synergistic effects and thus better responses by combining ionizing radiation with other anti-tumor treatments. Furthermore, multimodal therapies often have a balanced toxicity profile. To date, few studies have evaluated the effect of combination therapies with PRRT, some of them phase I/II trials. This review will focus on several clinically tested, tailored approaches to improving the effects of

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Soltis, Anthony, Boryana Zhelyazkova, Pascal Drane, et al. "High Throughput Microfluidics Platform to Assess Synthetic Lethality and Novel Therapeutic Drug Combinations." Blood 142, Supplement 1 (2023): 7139. http://dx.doi.org/10.1182/blood-2023-190651.

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Molecularly targeted therapies have reshaped cancer treatment in recent decades; however, not all patient cancers are eligible for or effectively treated by such approaches. In addition, resistance mechanisms (both pre-existing and acquired) limit clinical benefit. To these ends, combination therapies involving targeted agents are increasingly being developed for their potential to induce potent synthetic lethalities, bypass drug resistance, promote durable responses, limit adverse side effects via reduced dosing, and expand treatment options. In the context of acute myeloid leukemia (AML) spe

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Vakil, Vahideh, and Wade Trappe. "Drug Combinations: Mathematical Modeling and Networking Methods." Pharmaceutics 11, no. 5 (2019): 208. http://dx.doi.org/10.3390/pharmaceutics11050208.

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Treatments consisting of mixtures of pharmacological agents have been shown to have superior effects to treatments involving single compounds. Given the vast amount of possible combinations involving multiple drugs and the restrictions in time and resources required to test all such combinations in vitro, mathematical methods are essential to model the interactive behavior of the drug mixture and the target, ultimately allowing one to better predict the outcome of the combination. In this review, we investigate various mathematical methods that model combination therapies. This survey includes

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Thompson, Zachary J., Jamie K. Teer, Jiannong Li, et al. "Drepmel—A Multi-Omics Melanoma Drug Repurposing Resource for Prioritizing Drug Combinations and Understanding Tumor Microenvironment." Cells 11, no. 18 (2022): 2894. http://dx.doi.org/10.3390/cells11182894.

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Although substantial progress has been made in treating patients with advanced melanoma with targeted and immuno-therapies, de novo and acquired resistance is commonplace. After treatment failure, therapeutic options are very limited and novel strategies are urgently needed. Combination therapies are often more effective than single agents and are now widely used in clinical practice. Thus, there is a strong need for a comprehensive computational resource to define rational combination therapies. We developed a Shiny app, DRepMel to provide rational combination treatment predictions for melano

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Margaryan, Hasmik, Dimitrios D. Evangelopoulos, Leticia Muraro Wildner, and Timothy D. McHugh. "Pre-Clinical Tools for Predicting Drug Efficacy in Treatment of Tuberculosis." Microorganisms 10, no. 3 (2022): 514. http://dx.doi.org/10.3390/microorganisms10030514.

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Combination therapy has, to some extent, been successful in limiting the emergence of drug-resistant tuberculosis. Drug combinations achieve this advantage by simultaneously acting on different targets and metabolic pathways. Additionally, drug combination therapies are shown to shorten the duration of therapy for tuberculosis. As new drugs are being developed, to overcome the challenge of finding new and effective drug combinations, systems biology commonly uses approaches that analyse mycobacterial cellular processes. These approaches identify the regulatory networks, metabolic pathways, and

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Conway, Brian, and Bluma G. Brenner. "Can simplified antiretroviral drug combination therapies resist resistance?" AIDS 36, no. 11 (2022): 1597–98. http://dx.doi.org/10.1097/qad.0000000000003308.

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Henry, Mitchell L., Victor D. Bowers, Bruce G. Sommer, and Ronald M. Ferguson. "Combination drug therapies for immunosuppression in renal transplantation." Transplantation Reviews 2 (January 1988): 55–76. http://dx.doi.org/10.1016/s0955-470x(88)80006-5.

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Pontón, Iris, Andrea Martí del Rio, Marta Gómez Gómez, and David Sánchez-García. "Preparation and Applications of Organo-Silica Hybrid Mesoporous Silica Nanoparticles for the Co-Delivery of Drugs and Nucleic Acids." Nanomaterials 10, no. 12 (2020): 2466. http://dx.doi.org/10.3390/nano10122466.

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Combination therapies rely on the administration of more than one drug, with independent mechanisms of action, aiming to enhance the efficiency of the treatment. For an optimal performance, the implementation of such therapies requires the delivery of the correct combination of drugs to a specific cellular target. In this context, the use of nanoparticles (NP) as platforms for the co-delivery of multiple drugs is considered a highly promising strategy. In particular, mesoporous silica nanoparticles (MSN) have emerged as versatile building blocks to devise complex drug delivery systems (DDS). T

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Xiao, Xiao, James Trevor Oswald, Ting Wang, Weina Zhang, and Wenliang Li. "Use of Anticancer Platinum Compounds in Combination Therapies and Challenges in Drug Delivery." Current Medicinal Chemistry 27, no. 18 (2020): 3055–78. http://dx.doi.org/10.2174/0929867325666181105115849.

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As one of the leading and most important metal-based drugs, platinum-based pharmaceuticals are widely used in the treatment of solid malignancies. Despite significant side effects and acquired drug resistance have limited their clinical applications, platinum has shown strong inhibitory effects for a wide assortment of tumors. Drug delivery systems using emerging technologies such as liposomes, dendrimers, polymers, nanotubes and other nanocompositions, all show promise for the safe delivery of platinum-based compounds. Due to the specificity of nano-formulations; unwanted side-effects and dru

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De Los Santos, Maria Ana Isabel C., Anne-Florence Blandin, Alejandra E. Aguilar, et al. "Abstract 6732: Identifying novel combination therapies for Ewing sarcoma." Cancer Research 83, no. 7_Supplement (2023): 6732. http://dx.doi.org/10.1158/1538-7445.am2023-6732.

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Abstract Ewing sarcoma is the second most common pediatric bone cancer in children and young adults. The standard of care therapy consists of chemotherapy, surgery, and radiation. Despite therapeutic advances, metastatic and relapsed Ewing sarcoma have poor outcomes. This is partially because transcription factors, such as the Ewing sarcoma oncoprotein EWS-FLI1, are difficult targets for the development of small molecules. Novel synergistic combination treatments are needed, and drug repurposing efforts can fast track potential therapies into clinical trials. To identify synergistic anti-Ewing

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Narayan, Ravi, Piet Molenaar, Fleur Cornelissen, Tom Wurdinger, Jan Koster, and Bart Westerman. "COMP-09. A CANCER DRUG ATLAS ENABLES PREDICTION OF PARALLEL DRUG VULNERABILITIES OF GLIOBLASTOMA." Neuro-Oncology 21, Supplement_6 (2019): vi62—vi63. http://dx.doi.org/10.1093/neuonc/noz175.252.

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Abstract Personalized cancer treatments using synergistic combinations of drugs is attractive but proves to be highly challenging. The combinatorial nature of such problems results in an enormous parameter space that cannot be resolved by empirical research, i.e. testing all combinations for all molecularly defined tumors. In addition, effective drug synergy is hard to predict. Here we present an approach to map data of drug-response encyclopedias and represent these as a drug atlas. This atlas consists of a framework of chemotherapeutic responses that represents a drug vulnerability landscape

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Du, Jian, and Xiaoying Li. "A Knowledge Graph of Combined Drug Therapies Using Semantic Predications From Biomedical Literature: Algorithm Development." JMIR Medical Informatics 8, no. 4 (2020): e18323. http://dx.doi.org/10.2196/18323.

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Background Combination therapy plays an important role in the effective treatment of malignant neoplasms and precision medicine. Numerous clinical studies have been carried out to investigate combination drug therapies. Automated knowledge discovery of these combinations and their graphic representation in knowledge graphs will enable pattern recognition and identification of drug combinations used to treat a specific type of cancer, improve drug efficacy and treatment of human disorders. Objective This paper aims to develop an automated, visual approach to discover knowledge about combination

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Hwangbo, Haeun, Sarah Patterson, Andy Dai, Deborah Plana, and Adam C. Palmer. "Abstract 5718: Additivity predicts the clinical efficacy of most approved combination therapies for advanced cancer." Cancer Research 83, no. 7_Supplement (2023): 5718. http://dx.doi.org/10.1158/1538-7445.am2023-5718.

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Abstract Most advanced cancers are treated with drug combinations. Rational designs aim to identify synergistic drug interactions to produce superior treatments. However, metrics of drug interaction (i.e., synergy, additivity, antagonism) apply to pre-clinical experiments, and there has been no established method to quantify synergy versus additivity in clinical settings. Here, we propose and apply a model of drug additivity for progression-free survival (PFS) to assess if the clinical efficacies of approved drug combinations are more than, or equal to, the sum of their parts. This model accou

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Kucukosmanoglu, Asli, Silvia Scoarta, Thomas Wijnands, et al. "Abstract 6312: The adverse events atlas, towards a strategy to predict synergistic adverse events of combination therapies." Cancer Research 82, no. 12_Supplement (2022): 6312. http://dx.doi.org/10.1158/1538-7445.am2022-6312.

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Abstract The current gold-standard of estimating adverse events of a drug are clinical trials. However, these trials fail to represent real-life practice where patients have additional diseases (comorbidities) and commonly use numerous drugs when entering the clinic. Therefore, there is a rise of interest in combinational therapies, also because effective combinations are expected to prevent therapy resistance. At this moment it is not feasible to predict the adverse events of new combination therapies due to lack of available information both from a dimensionality (i.e., number of adverse eve

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Jin, Wengong, Jonathan M. Stokes, Richard T. Eastman, et al. "Deep learning identifies synergistic drug combinations for treating COVID-19." Proceedings of the National Academy of Sciences 118, no. 39 (2021): e2105070118. http://dx.doi.org/10.1073/pnas.2105070118.

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Effective treatments for COVID-19 are urgently needed. However, discovering single-agent therapies with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been challenging. Combination therapies play an important role in antiviral therapies, due to their improved efficacy and reduced toxicity. Recent approaches have applied deep learning to identify synergistic drug combinations for diseases with vast preexisting datasets, but these are not applicable to new diseases with limited combination data, such as COVID-19. Given that drug synergy often occurs through inh

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Schlachter, Noah M., Eric J. Miller, Jonathan F. Anker, Matthew D. Galsky, and Adam C. Palmer. "Abstract B011: Predictable successes: drug additivity explains the efficacy of combination therapies for metastatic urothelial cancer." Clinical Cancer Research 30, no. 10_Supplement (2024): B011. http://dx.doi.org/10.1158/1557-3265.bladder24-b011.

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Abstract Objective: Combination drug regimens have changed the treatment landscape of metastatic urothelial cancer (mUC) and other cancers and are integrated into routine clinical practice. Combination drug regimens may impact cancer outcomes via three major pharmacologic principles: less-than-additive, additive, or more-than-additive efficacy (i.e., synergy). Despite the profound implications of these types of interactions on future drug and biomarker development, as well as on treatment sequencing, these principles have been underexplored in contemporary clinical trials. Here we analyze rece

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Zhang, Hongbo, Wenguo Cui, Xiangmeng Qu, et al. "Photothermal-responsive nanosized hybrid polymersome as versatile therapeutics codelivery nanovehicle for effective tumor suppression." Proceedings of the National Academy of Sciences 116, no. 16 (2019): 7744–49. http://dx.doi.org/10.1073/pnas.1817251116.

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Effective cancer therapies often demand delivery of combinations of drugs to inhibit multidrug resistance through synergism, and the development of multifunctional nanovehicles with enhanced drug loading and delivery efficiency for combination therapy is currently a major challenge in nanotechnology. However, such combinations are more challenging to administer than single drugs and can require multipronged approaches to delivery. In addition to being stable and biodegradable, vehicles for such therapies must be compatible with both hydrophobic and hydrophilic drugs, and release drugs at susta

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Soltis, Anthony R., Boryana Zhelyazkova, Pascal Drane, et al. "Abstract 3900: A high-throughput platform identifies novel drug combinations towards acute myeloid leukemia therapy." Cancer Research 84, no. 6_Supplement (2024): 3900. http://dx.doi.org/10.1158/1538-7445.am2024-3900.

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Abstract Molecularly targeted therapies have reshaped oncology in recent decades, though not all patients are eligible for such treatments and resistance mechanisms limit clinical benefit. In response, combination therapies, which can induce potent synthetic lethalities, bypass drug resistance, and expand treatment options, are increasingly being developed. A major hurdle limiting novel combination therapy discovery is the sheer combinatorics associated with broadly testing two or more agents. Thus, there is a practical need for methodologies that prioritize test compounds and technologies for

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Acosta-Vélez, Giovanny, Chase Linsley, Timothy Zhu, Willie Wu, and Benjamin Wu. "Photocurable Bioinks for the 3D Pharming of Combination Therapies." Polymers 10, no. 12 (2018): 1372. http://dx.doi.org/10.3390/polym10121372.

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Combination therapies mediate drug synergy to improve treatment efficacy and convenience, leading to higher levels of compliance. However, there are challenges with their manufacturing as well as reduced flexibility in dosing options. This study reports on the design and characterization of a polypill fabricated through the combination of material jetting and binder jetting for the treatment of hypertension. The drugs lisinopril and spironolactone were loaded into hydrophilic hyaluronic acid and hydrophobic poly(ethylene glycol) (PEG) photocurable bioinks, respectively, and dispensed through a

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Radke, Katarzyna, Karin Hansson, Jani Saarela, et al. "Abstract 3892: High-throughput combination screen for identifying novel therapies against high-risk neuroblastoma." Cancer Research 82, no. 12_Supplement (2022): 3892. http://dx.doi.org/10.1158/1538-7445.am2022-3892.

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Abstract Neuroblastoma is a childhood solid tumor commonly located in the adrenal gland. High-risk neuroblastoma patients undergo multidrug and multi-interventional treatment but despite these efforts many patients develop resistance to chemotherapy and eventually relapse. Neuroblastoma patients face an urgent need of novel therapeutic strategies that could effectively combat the disease. In a recent study we identified kinesin spindle protein (KSP) as a highly effective target in high-risk neuroblastoma. Pharmacological inhibition of KSP resulted in complete regression of a subset of neurobla

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Pulkkinen, Otto I., Prson Gautam, Ville Mustonen, and Tero Aittokallio. "Multiobjective optimization identifies cancer-selective combination therapies." PLOS Computational Biology 16, no. 12 (2020): e1008538. http://dx.doi.org/10.1371/journal.pcbi.1008538.

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Combinatorial therapies are required to treat patients with advanced cancers that have become resistant to monotherapies through rewiring of redundant pathways. Due to a massive number of potential drug combinations, there is a need for systematic approaches to identify safe and effective combinations for each patient, using cost-effective methods. Here, we developed an exact multiobjective optimization method for identifying pairwise or higher-order combinations that show maximal cancer-selectivity. The prioritization of patient-specific combinations is based on Pareto-optimization in the sea

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Madamsetty, Vijay Sagar, Krishnendu Pal, Shamit Kumar Dutta, Enfeng Wang, and Debabrata Mukhopadhyay. "Targeted Dual Intervention-Oriented Drug-Encapsulated (DIODE) Nanoformulations for Improved Treatment of Pancreatic Cancer." Cancers 12, no. 5 (2020): 1189. http://dx.doi.org/10.3390/cancers12051189.

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Despite recent advancements, effective treatment for pancreatic ductal adenocarcinoma (PDAC) has remained elusive. The overall survival rate in PDAC patients has been dismally low due to resistance to standard therapies. In fact, the failure of monotherapies to provide long-term survival benefits in patients led to ascension of several combination therapies for PDAC treatment. However, these combination therapies provided modest survival improvements while increasing treatment-related adverse side effects. Hence, recent developments in drug delivery methods hold the potential for enhancing the

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Palmer, Adam C., Benjamin Izar, Haeun Hwangbo, and Peter K. Sorger. "Predictable Clinical Benefits without Evidence of Synergy in Trials of Combination Therapies with Immune-Checkpoint Inhibitors." Clinical Cancer Research 28, no. 2 (2022): 368–77. http://dx.doi.org/10.1158/1078-0432.ccr-21-2275.

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Abstract Purpose: Combinations of immune-checkpoint inhibitors (ICI) with other cancer therapies have been approved for advanced cancers in multiple indications, and numerous trials are under way to test new combinations. However, the mechanisms that account for the superiority of approved ICI combinations relative to their constituent monotherapies remain unknown. Experimental Design: We analyzed 13 phase III clinical trials testing combinations of ICIs with each other or other drugs in patients with advanced melanoma and lung, breast, gastric, kidney, and head and neck cancers. The clinical

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Boccella, Serena, Lidia De Filippis, Cristina Giorgio, et al. "Combination Drug Therapy for the Management of Chronic Neuropathic Pain." Biomolecules 13, no. 12 (2023): 1802. http://dx.doi.org/10.3390/biom13121802.

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Chronic neuropathic pain (NP) is an increasingly prevalent disease and leading cause of disability which is challenging to treat. Several distinct classes of drugs are currently used for the treatment of chronic NP, but each drug targets only narrow components of the underlying pathophysiological mechanisms, bears limited efficacy, and comes with dose-limiting side effects. Multimodal therapies have been increasingly proposed as potential therapeutic approaches to target the multiple mechanisms underlying nociceptive transmission and modulation. However, while preclinical studies with combinat

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Vandamme, A.-M., K. Van Vaerenbergh, and E. De Clercq. "Anti-Human Immunodeficiency Virus Drug Combination Strategies." Antiviral Chemistry and Chemotherapy 9, no. 3 (1998): 187–203. http://dx.doi.org/10.1177/095632029800900301.

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It is now generally accepted that mono- and bitherapy for human immunodeficiency virus type 1 (HIV-1) infection are only transiently efficient mainly due to virus drug resistance. To obtain a sustained benefit from antiviral therapy, current guidelines recommend at least triple-drug combinations, or the so-called highly active antiretroviral therapy (HAART). In some patients, HAART can be problematic, either because it is difficult to remain compliant or because previous suboptimum therapies have limited the choice of drugs. For compliant drug-naive patients, HAART should be able to offer long

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Hwangbo, Haeun, and Adam C. Palmer. "Abstract A135: Are survival benefits of new drugs in combinations due to modest benefits in most patients or large benefits in few patients?" Molecular Cancer Therapeutics 22, no. 12_Supplement (2023): A135. http://dx.doi.org/10.1158/1535-7163.targ-23-a135.

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Abstract INTRODUCTION Combination therapy is a cornerstone in cancer treatment, often developed by adding new therapies to a standard-of-care treatment. However, clinical trials of adding a drug to a combination (A versus A+B) face an ambiguity in interpretation, because a higher Kaplan-Meier survival curve can result from modest benefits to overall survival (OS) or progression-free survival (PFS) in most patients, or from larger benefits in a few patients. This ambiguity exists even with complete patient data because no individual patient is simultaneous enrolled in control and test arms. Thu

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Li, Xinran, Angel S. N. Ng, Victor C. Y. Mak, Karen K. L. Chan, Annie N. Y. Cheung, and Lydia W. T. Cheung. "Strategic Combination Therapies for Ovarian Cancer." Current Cancer Drug Targets 20, no. 8 (2020): 573–85. http://dx.doi.org/10.2174/1568009620666200511084007.

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Ovarian cancer remains the leading cause of gynecologic cancer-related deaths among women worldwide. The dismal survival rate is partially due to recurrence after standardized debulking surgery and first-line chemotherapy. In recent years, targeted therapies, including antiangiogenic agents or poly (ADP-ribose) polymerase inhibitors, represent breakthroughs in the treatment of ovarian cancer. As more therapeutic agents become available supplemented by a deeper understanding of ovarian cancer biology, a range of combination treatment approaches are being actively investigated to further improve

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Tiek, Deanna, and Shi-Yuan Cheng. "DNA damage and metabolic mechanisms of cancer drug resistance." Cancer Drug Resistance 5, no. 2 (2022): 368–79. http://dx.doi.org/10.20517/cdr.2021.148.

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Cancer drug resistance is one of the main barriers to overcome to ensure durable treatment responses. While many pivotal advances have been made in first combination therapies, then targeted therapies, and now broadening out to immunomodulatory drugs or metabolic targeting compounds, drug resistance is still ultimately universally fatal. In this brief review, we will discuss different strategies that have been used to fight drug resistance from synthetic lethality to tumor microenvironment modulation, focusing on the DNA damage response and tumor metabolism both within tumor cells and their su

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Saputra, Elysia, and Lisa Tucker-Kellogg. "Abstract B026: Simulations of cancer evolution predict relative benefits of synergistic and non-synergistic drug combinations for combating different landscapes of drug-resistance." Cancer Research 82, no. 10_Supplement (2022): B026. http://dx.doi.org/10.1158/1538-7445.evodyn22-b026.

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Abstract Cancer therapies often have short duration of success due to the development of drug-resistance, which motivates research into anti-evolutionary therapies. A popular strategy is to combine two drugs, particularly if they have synergistic (greater-than-additive) efficacy. However, therapies that cause synergistic suppression of drug-sensitive cells will also suffer from synergistic release of drug-resistant cells, when drug-resistance arises. Not yet understood is the impact of partial drug-resistance and semi-resistant phenotypes on the speed of clonal expansion under combination ther

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Weinberg Sibony, Roni, Omri Segev, Saar Dor, and Itamar Raz. "Drug Therapies for Diabetes." International Journal of Molecular Sciences 24, no. 24 (2023): 17147. http://dx.doi.org/10.3390/ijms242417147.

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The treatment of type 2 diabetes (T2D) necessitates a multifaceted approach that combines behavioral and pharmacological interventions to mitigate complications and sustain a high quality of life. Treatment encompasses the management of glucose levels, weight, cardiovascular risk factors, comorbidities, and associated complications through medication and lifestyle adjustments. Metformin, a standard in diabetes management, continues to serve as the primary, first-line oral treatment across all age groups due to its efficacy, versatility in combination therapy, and cost-effectiveness. Glucagon-l

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Biskupiak, Zack, Victor Vinh Ha, Aarushi Rohaj, and Grzegorz Bulaj. "Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases." Journal of Clinical Medicine 13, no. 2 (2024): 403. http://dx.doi.org/10.3390/jcm13020403.

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Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization of adjunct DTx by the US Food and Drug Administration and draft guidelines on “prescription drug use-related software” illustrate opportunities to create drug + digital combination therapies, ultimately leading towards drug–device combination products (DTx has a status of medical devices). Digital interventions (mobile, web-based, virtual reality, and

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Martinelli, A., R. Moreira, and P. Cravo. "Malaria Combination Therapies: Advantages and Shortcomings." Mini-Reviews in Medicinal Chemistry 8, no. 3 (2008): 201–12. http://dx.doi.org/10.2174/138955708783744092.

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Mrowka, Piotr, та Eliza Glodkowska-Mrowka. "PPARγ Agonists in Combination Cancer Therapies". Current Cancer Drug Targets 20, № 3 (2020): 197–215. http://dx.doi.org/10.2174/1568009619666191209102015.

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: Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor acting as a transcription factor involved in the regulation of energy metabolism, cell cycle, cell differentiation, and apoptosis. These unique properties constitute a strong therapeutic potential that place PPARγ agonists as one of the most interesting and widely studied anticancer molecules. : Although PPARγ agonists exert significant, antiproliferative and tumoricidal activity in vitro, their anticancer efficacy in animal models is ambiguous, and their effectiveness in clinical trials in monotherapy is unsatisf

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Carter, Monique, and Saima Khan. "Novel–novel fixed-dose combination therapies." Nature Reviews Drug Discovery 18, no. 6 (2019): 413. http://dx.doi.org/10.1038/d41573-019-00066-z.

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van Hasselt, J. G. Coen, and Ravi Iyengar. "Systems Pharmacology: Defining the Interactions of Drug Combinations." Annual Review of Pharmacology and Toxicology 59, no. 1 (2019): 21–40. http://dx.doi.org/10.1146/annurev-pharmtox-010818-021511.

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The majority of diseases are associated with alterations in multiple molecular pathways and complex interactions at the cellular and organ levels. Single-target monotherapies therefore have intrinsic limitations with respect to their maximum therapeutic benefits. The potential of combination drug therapies has received interest for the treatment of many diseases and is well established in some areas, such as oncology. Combination drug treatments may allow us to identify synergistic drug effects, reduce adverse drug reactions, and address variability in disease characteristics between patients.

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Ashok, Chakraborty1#* and Anil Diwan2#. "Pharmacodynamics of Remdesivir: How to Improve for COVID-19 Treatment." Journal of Biomedical Research & Environmental Sciences 1, no. 8 (2020): 431–38. https://doi.org/10.37871/jbres1175.

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Potential clinical benefi t in SARS-CoV-2 infection upon remdesivir treatment has been established. Recently, FDA has granted full approval for the clinical use of remdesivir for COVID therapy. However, the effi cacy of remdesivir alone or in combination with other antivirals is still open to research, especially in terms of benefi ts vs. risk ratio. We here review remdesivir therapy based on a search for relevant pharmacological evidences with regards to the Pharmacokinetics (PK) and Pharmacodynamics (PD) of appropriate antiviral compounds against COVID-19 alone or in combination with other p

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