The Team

Pictured left to right:
Alastair Kyle | Jennifer Baker | Lynsey Huxham | Kirstin Lindquist | Jonathan Sy | Andrew Minchinton

Students past and present:
Erin Gabriel | Jordan Cran | Erin Flanagan | Misa Noda | Stephen Methot | Firas Moosvi | Sally Sun
Kirsten Bartels | Mayu Sasaki | Ben Lee | Katherine Thain | Krista McNicol | Lani Nykilchuk
Devon Yeoman

Research interests

Tumour Microenvironment and Extravascular Penetration

Our lab is interested in how the heterogeneous tumour vasculature and microenvironment impacts the delivery and efficacy of anti-cancer therapy.In contrast to most normal tissues, the tumour microenvironment is highly variable, and is characterized by sparse or aberrant vasculature and deregulated cell proliferation and death processes which combine to create gradients in biologically important molecules such as oxygen and glucose.

As a result, tumor cells can be located up to 15-20 cells away from the nearest blood vessel (more in some cases) in heterogeneous microregional environments.

Little is known regarding the ability of many of the most commonly used anticancer drugs to distribute within solid tumours. Measurement of gross tumor drug accumulation is a routine component of new drug development but reveals little about extravascular drug distribution.

Tumour Mapping

Recent advances in immunohistochemistry, robotic microscopy and computing have now made it feasible to scan entire tumour cryosections and quantitatively map drugs and immunostained biological markers relative to each other. For example, simultaneous mapping of radiolabelled or immunodetected drugs and tumour vasculature allows for evaluation of drug penetration as a function of distance from vasculature.

Additional markers for blood flow, hypoxia (pimonidazole), proliferation (BrdUrd, Ki67, PCNA), apoptosis (TUNEL, caspase 3) and DNA damage (gamma-H2AX) can be used to map the microregional effect of drugs in tumours. The recent development of anti-cancer agents that target existing tumour vasculature or the growth of new blood vessels undergoing angiogenesis can also be investigated by determining drug effects on distinct vascular populations identified for characteristics such as perfusion (intravenously administered fluorescent dyes), and maturity (collagen type IV, αSMA, pericytes).

Multilayered Cell Cultures (MCCs)

Our laboratory has also pioneered the development of an in vitro tissue engineered model of solid tumours, multilayered cell cultures (MCCs), which we use to quantitatively examine the interaction of anticancer drugs in tissue layers. This technique, in combination with quantitative microscopy and image analysis is used to model the distribution of drugs and their microregional effects within the extravascular compartment of tumours.

Minchinton Lab Photos