Modeling Multiscale Necrotic and Calcified Tissue Biomechanics in Cancer Patients: Application to Ductal Carcinoma In Situ (DCIS)

Abstract

Tissue necrosis and calcification significantly affect cancer progression and clinical treatment decisions. Necrosis and calcification are inherently multiscale processes, operating at molecular to tissue scales with time scales ranging from hours to months. This chapter details key insights we have gained through mechanistic continuum and discrete multiscale models, including the first modeling of necrotic cell swelling, lysis, and calcification. Among our key findings: necrotic volume loss contributes to steady tumor sizes but can destabilize tumor morphology; steady necrotic fractions can emerge even during unstable growth; necrotic volume loss is responsible for linear ductal carcinoma in situ (DCIS) growth; fast necrotic cell swelling creates mechanical tears at the perinecrotic boundary; multiscale interactions give rise to an age-structured, stratified necrotic core; and mechanistic, patient-calibrated DCIS modeling allows us to assess our working biological assumptions and better interpret pathology and mammography. We finish by outlining our integrative computational oncology approach to developing computational tools that we hope will one day assist clinicians and patients in their treatment decisions.