scholarly journals Improving mathematical models of cancer by including resistance to therapy: a study in non-small cell lung cancer

2021 ◽  
Author(s):  
Virginia Ardévol Martinez ◽  
Narmin Ghaffari Laleh ◽  
Monica Salvioli ◽  
Frank Thuijsman ◽  
Joel S. Brown ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Therapy Resistance ◽  
Tumor Burden ◽  
Small Cell ◽  
Theoretic Model ◽  
Small Cell Lung ◽  
Game Theoretic ◽  
Game Theoretic Model

In this paper, a large dataset of 590 Non-Small Cell Lung Patients treated with either chemotherapy or immunotherapy was used to determine whether a game-theoretic model including both evolution of therapy resistance and cost of resistance provides a better fit than classical mathematical models of population growth (exponential, logistic, classic Bertalanffy, general Bertalanffy, Gompertz, general Gompertz). This is the first time a large clinical patient cohort (as opposed to only in-vitro data) has been used to apply a game-theoretic cancer model. The game-theoretic model provides a better fit to the tumor dynamics of the 590 Non-Small Cell Lung Cancer patients than any of the non-evolutionary population growth models. This is not simply due to having more parameters in the game-theoretic model. The game-theoretic model is able to fit accurately patients whose tumor burden exhibit a U-shaped trajectory over time. We then demonstrate how this game-theoretic model provides predictions of tumor growth based on just a few initial measurements. Assuming that treatment-specific parameters define the treatment impact completely, we then explore alternative treatment protocols and their impact on the tumor growth. As such, the model can be used to suggest patient-specific optimal treatment regimens with the goal of minimizing final tumor burden. Therapeutic protocols based on game-theoretic modeling can predict tumor growth, and improve patient outcome. The model invites evolutionary therapies that anticipate and steer the evolution of therapy resistance.

Plain language summary of the CROWN study comparing lorlatinib with crizotinib for people with untreated non-small cell lung cancer

2021 ◽  
Author(s):  
Benjamin J Solomon ◽  
Todd M Bauer ◽  
Filippo de Marinis ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Side Effects ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Research Study ◽  
Small Cell ◽  
Plain Language ◽  
Small Cell Lung

This is a summary of a research study (known as a clinical trial) called CROWN. The study tested two medicines called lorlatinib and crizotinib in participants with untreated non-small cell lung cancer that had spread to other parts of their body. All those who took part had changes in a gene called ALK, which is involved in cell growth. In total, 296 participants from 23 countries took part. Half the participants took lorlatinib and half took crizotinib. After participants started taking lorlatinib or crizotinib, they were checked regularly to see if their tumors had grown or spread to other parts of their body (known as tumor progression) and to monitor any side effects. After 1 year of treatment, the participants who took lorlatinib were twice as likely to be alive with no tumor growth as the participants who took crizotinib. More participants who took lorlatinib had cancer that shrank (76%) compared with the participants who took crizotinib (58%). This was also true of the participants whose cancer had spread to their brain. The most common side effects in participants who took lorlatinib were increases in the amount of cholesterol and triglycerides (a type of fat) in their blood, swelling, weight gain, nerve damage, unclear thoughts, and diarrhea. Among the participants who took crizotinib, the most common side effects were diarrhea, feeling like you want to throw up, sight problems, swelling, vomiting, changes in liver function, and feeling tired. Overall, the CROWN study showed that fewer participants with advanced ALK+ non-small cell lung cancer died or had tumor growth with lorlatinib compared with crizotinib treatment. ClinicalTrials.gov NCT number: NCT03052608 .

scholarly journals Establishment of a non-small-cell lung cancer-liver metastasis patient-derived tumor xenograft model for the evaluation of patient-tailored chemotherapy

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Xue Yang ◽  
Gaopei Meng
Keyword(s):  
Lung Cancer ◽  
Liver Metastasis ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Tumor Xenograft ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Ifn Γ

Abstract In order to optimize patient-tailored chemotherapy, a non-small-cell lung cancer (NSCLC)-liver metastasis patient-derived tumor xenograft (PDTX) model is developed. Computed tomography (CT)-guided NSCLC percutaneous biopsy was subcutaneously inoculated into the flank of non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice (PDTX F1) and allowed to reach 500 mm3 volume. Then, the tumors were re-transplanted into Balb/c nude mice and liver metastasis was confirmed (PDTX F2), which were further assigned into doxorubicin (DOX), docetaxel (DTX), and non-treatment control group. H&E staining and Keratin 20 (CK20) staining were applied to determine the consistency of PDTX models and primary tumors. Tumor growth curve, body weight, and the expression of p65 nuclear factor (NF)-κB and the secretion of interferon (IFN)-γ were investigated. The successive transplant procedure can induce the NSCLC-liver metastasis PDTX model, and morphological and structural characteristics of PDTX models (F2) were in accordance with primary tumors. DOX and DTX could delay tumor growth, activate the NF-κB pathway, and promote IFN-γ secretion in the PDTX models. The NSCLC-liver metastasis PDTX model is established and provides a powerful mean to assess chemotherapeutic efficacy.

scholarly journals Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer

2019 ◽  
Vol 51 (8) ◽  
pp. 1-13 ◽  
Author(s):  
Dong Ha Kim ◽  
HyeongRyul Kim ◽  
Yun Jung Choi ◽  
Seon Ye Kim ◽  
Jung-Eun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Escape ◽  
Small Cell ◽  
Small Cell Lung
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