A convex optimization approach to cancer treatment to address tumor heterogeneity and imperfect drug penetration in physiological compartments

Giulia Giordano, Anders Rantzer, Vanessa D. Jonsson

Research output: Chapter in Book/Conference proceedings/Edited volumeConference contributionScientificpeer-review

11 Citations (Scopus)

Abstract

The clinical success of targeted cancer therapies is limited by the emergence of drug resistance often due to pre-existing tumor genetic heterogeneity and acquired, therapy-induced resistance. Targeted therapies have varied success in addressing metastatic disease, due to their ability to penetrate certain physiological compartments. This paper considers an evolutionary cancer model that incorporates tumor cell growth, mutation and compartmental migration and leverages recent results on the optimal control of monotone and convex systems to synthesize switching treatment strategies where a single drug or a predetermined combination of drugs is used at a given time. The need for switching is motivated by clinical considerations such as the limited effectiveness of any single targeted therapy against multiple resistance mechanisms arising in a single patient and the inability to design drug combinations at effective doses due to toxicity constraints. An optimal and clinically feasible switching therapy is obtained as the solution of a convex optimization problem that exploits the diagonally-dominant structure of the model. We demonstrate that this method yields an effective strategy in mitigating disease evolution in the presence of imperfect drug penetration in two compartments on an experimentally identified model of anaplastic lymphoma kinase (ALK)-rearranged lung carcinoma.

Original languageEnglish
Title of host publication2016 IEEE 55th Conference on Decision and Control, CDC 2016
PublisherInstitute of Electrical and Electronics Engineers (IEEE)
Pages2494-2500
Number of pages7
ISBN (Electronic)9781509018376
DOIs
Publication statusPublished - 27 Dec 2016
Externally publishedYes
Event55th IEEE Conference on Decision and Control, CDC 2016 - Las Vegas, United States
Duration: 12 Dec 201614 Dec 2016

Conference

Conference55th IEEE Conference on Decision and Control, CDC 2016
Abbreviated titleCDC 2016
Country/TerritoryUnited States
CityLas Vegas
Period12/12/1614/12/16

Fingerprint

Dive into the research topics of 'A convex optimization approach to cancer treatment to address tumor heterogeneity and imperfect drug penetration in physiological compartments'. Together they form a unique fingerprint.

Cite this