When eradication is impossible, cancer treatment aims to delay the emergence of resistance while minimizing cancer burden and treatment. Adaptive therapies may achieve these aims, with success based on three assumptions: resistance is costly, sensitive cells compete with resistant cells, and therapy reduces the population of sensitive cells. We use a range of mathematical models and treatment strategies to investigate the tradeoff between controlling cell populations and delaying the emergence of resistance. These models extend game theoretic and competition models with four additional components: 1) an Allee effect where cell populations grow more slowly at low population sizes, 2) healthy cells that compete with cancer cells, 3) immune cells that suppress cancer cells, and 4) resource competition for a growth factor like androgen. In comparing maximum tolerable dose, intermittent treatment, and adaptive therapy strategies, no therapeutic choice robustly breaks the three-way tradeoff among the three therapeutic aims. Almost all models show a tight tradeoff between time to emergence of resistant cells and cancer cell burden, with intermittent and adaptive therapies following identical curves. For most models, some adaptive therapies delay overall tumor growth more than intermittent therapies, but at the cost of higher cell populations. The Allee effect breaks these relationships, with some adaptive therapies performing poorly due to their failure to treat sufficiently to drive populations below the threshold. When eradication is impossible, no treatment can simultaneously delay emergence of resistance, limit total cancer cell numbers, and minimize treatment. Simple mathematical models can play a role in designing the next generation of therapies that balance these competing objectives.
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http://dx.doi.org/10.3934/mbe.2021315 | DOI Listing |
Discov Oncol
December 2024
Department of Critical Care Medicine, The Fifth People's Hospital of Ganzhou City, Ganzhou, 341000, China.
Lung adenocarcinoma (LUAD) is a major contributor to cancer-related deaths, distinguished by its pronounced tumor heterogeneity and persistent challenges in overcoming drug resistance. In this study, we utilized single-cell RNA sequencing (scRNA-seq) to dissect the roles of programmed cell death (PCD) pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis, in shaping LUAD heterogeneity, immune infiltration, and prognosis. Among these, ferroptosis and pyroptosis were most significantly associated with favorable survival outcomes, highlighting their potential roles in enhancing anti-tumor immunity.
View Article and Find Full Text PDFJ Manag Care Spec Pharm
December 2024
Health Economics and Value Assessment, Sanofi, Boston, MA.
Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening thrombotic microangiopathy. Caplacizumab is the only treatment approved by the European Medicines Agency and the US Food and Drug Administration for iTTP, to be given in combination with plasma exchange therapy (PEX) and immunosuppression (IS). The National Institute for Health and Care Excellence's independent appraisal committee assessed the cost-effectiveness of caplacizumab and concluded that the addition of caplacizumab to PEX+IS is cost-effective under a patient access scheme in the United Kingdom.
View Article and Find Full Text PDFNanoscale
December 2024
Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.
The convergence of nanotechnology and tissue engineering has paved the way for innovative cancer treatments that leverage the unique light absorption properties of nanomaterials. Indeed, photothermal therapy (PTT) and photodynamic therapy (PDT) utilize nanomaterials to convert near-infrared light into therapeutic energy for cancer treatment. This study focuses on the application of poly(lactic--glycolic acid) (PLGA) scaffolds, enhanced by graphene oxide, TiCT MXene, and TiS transition metal dichalcogenides for PDT and PTT treatments evaluated within 3D-bioprinted breast cancers.
View Article and Find Full Text PDFmBio
December 2024
College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, China.
Bacteriophages, known for their ability to kill bacteria, are hampered in their effectiveness because bacteria are able to rapidly develop resistance, thereby posing a significant challenge for the efficacy of phage therapy. The impact of evolutionary trajectories on the long-term success of phage therapy remains largely unclear. Herein, we conducted evolutionary experiments, genomic analysis, and CRISPR-mediated gene editing, to illustrate the evolutionary trajectory occurring between phages and their hosts.
View Article and Find Full Text PDFClin Psychol Psychother
December 2024
Faculty of Health, University of Canberra, Canberra, Australia.
Caregivers of young people with borderline personality disorder (BPD) or BPD features experience significant burden and distress and often lack effective coping strategies. A family environment of pervasive invalidation can contribute to the disorder and work against effective coping. Consequently, some psychotherapy interventions for young people with BPD or BPD features aim to incorporate caregivers in treatment to varying degrees.
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