Precision oncology using ex vivo technology: a step towards individualised cancer care?

Abstract

Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more emphasis is being placed on alternative drug discovery platforms, such as ex vivo approaches. Ex vivo approaches aim to embed biological relevance and inter-patient variability at an earlier stage of drug discovery, and to offer more precise treatment stratification for patients. However, these techniques also have a high potential to offer personalised therapies to patients, complementing and enhancing genomic medicine. Although an array of approaches are available to researchers, only a minority of techniques have made it through to direct patient treatment within robust clinical trials. Within this review, we discuss the current challenges to ex vivo approaches within clinical practice and summarise the contemporary literature which has directed patient treatment. Finally, we map out how ex vivo approaches could transition from a small-scale, predominantly research based technology to a robust and validated predictive tool. In future, these pre-clinical approaches may be integrated into clinical cancer pathways to assist in the personalisation of therapy choices and to hopefully improve patient experiences and outcomes.

Ex vivo therapeutic screening of metastatic cSCC: A review of methodological considerations for clinical implementation

“…Culturing conditions vary greatly, and there are no standardised protocols for ex vivo culture 65 . Tumour dissociates can be simply plated in flat‐bottomed plates, or cultured as spheroids in ultra‐low attachment plates or using the hanging‐drop method.…”

“…There has been little progress since, raising questions of feasibility and the amenability of cSCC to ex vivo culture. Indeed, difficulty in culturing, low‐throughput, and rapid tissue degradation are inherent to ex vivo culture and have likely hindered experimental progress 65 ; however, it is increasingly evident that TME and patient‐specific genomic features influence therapeutic response, which justifies and necessitates greater expansion of this approach to more tumours including metastatic cSCC.…”

“…More than 40 recent clinical trials have been reported, including many interventional. 65 Some success has been observed in the clinic, with the provision of effective therapeutics that would not otherwise be considered. For example, short-term dissociates from a rare metastatic parotid SCC were treated with more than 125 anti-cancer drugs, and high-content imaging identified HER2 inhibitors as the most efficacious ex vivo.…”

“…Culturing conditions vary greatly, and there are no standardised protocols for ex vivo culture. 65 Tumour dissociates can be simply plated in flat-bottomed plates, or cultured as spheroids in ultra-low attachment plates or using the hanging-drop method. More complex, physiologically recapitulative models see dissociates seeded into microfluidic chambers, with or without extracellular matrix support.…”

“…Despite promising reports of therapeutic responses detected in culture, validation of in vivo response can only be achieved by informing actual treatment by integration into a clinical trial. More than 40 recent clinical trials have been reported, including many interventional 65 . Some success has been observed in the clinic, with the provision of effective therapeutics that would not otherwise be considered.…”