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Anti-cancer treatment schedule optimization based on tumor dynamics modelling incorporating evolving resistance

Yin, Anyue (author)
Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.;Leiden Univ, Med Ctr, Leiden Network Personalized Therapeut, Leiden, Netherlands.
van Hasselt, Johan G. C. (author)
Leiden Univ, Leiden Acad Ctr Drug Res LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands.
Guchelaar, Henk-Jan (author)
Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.;Leiden Univ, Med Ctr, Leiden Network Personalized Therapeut, Leiden, Netherlands.
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Friberg, Lena (author)
Uppsala universitet,Institutionen för farmaci
Moes, Dirk Jan A. R. (author)
Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.;Leiden Univ, Med Ctr, Leiden Network Personalized Therapeut, Leiden, Netherlands.
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Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands;Leiden Univ, Med Ctr, Leiden Network Personalized Therapeut, Leiden, Netherlands. Leiden Univ, Leiden Acad Ctr Drug Res LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands. (creator_code:org_t)
2022-03-10
2022
English.
In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Quantitative characterization of evolving tumor resistance under targeted treatment could help identify novel treatment schedules, which may improve the outcome of anti-cancer treatment. In this study, a mathematical model which considers various clonal populations and evolving treatment resistance was developed. With parameter values fitted to the data or informed by literature data, the model could capture previously reported tumor burden dynamics and mutant KRAS levels in circulating tumor DNA (ctDNA) of patients with metastatic colorectal cancer treated with panitumumab. Treatment schedules, including a continuous schedule, intermittent schedules incorporating treatment holidays, and adaptive schedules guided by ctDNA measurements were evaluated using simulations. Compared with the continuous regimen, the simulated intermittent regimen which consisted of 8-week treatment and 4-week suspension prolonged median progression-free survival (PFS) of the simulated population from 36 to 44 weeks. The median time period in which the tumor size stayed below the baseline level (T-TS

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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