Impact of targeted neoadjuvant therapies in the treatment of solid organ tumours

Abstract

Background: The advent of affordable technologies to perform detailed molecular profiling of tumours has transformed understanding of the specific genetic events that promote carcinogenesis and which may be exploited therapeutically. The application of targeted therapeutics has led to improved outcomes in advanced disease and this approach is beginning to become established in the management of potentially curable disease for surgical patients.Methods: This review article focuses on recent developments in the management of operable cancers of the gastrointestinal (GI) tract, specifically discussing the currently available data that evaluate the incorporation of targeted therapies in this setting.Results: A variety of targeted molecules are now available as treatment options in the management of GI cancers. Most are aimed at growth inhibition by acting on cell surface targets or intracellular pathways. Treatment paradigms are gradually shifting towards more prevalent use of systemic treatment prior to surgical intervention for operable disease with the aim of tumour downsizing and improved rates of long-term cure.Conclusion: A large number of ongoing clinical trials are evaluating novel targeted agents as neoadjuvant therapy in operable GI tumours. Therefore, further progress in the management of early-stage disease will undoubtedly be made over the next few years as these trials continue to report potentially practice-changing results.

New‐age surgical oncology

“…While not providing an answer, other than to suggest that surgeons need to be aware of this new ‘4th pillar of cancer therapy’, it is interesting to contemplate the future of cancer surgery. When we add in the expanding use of other systemic therapies, such as targeted therapies with monoclonal antibodies and tyrosine kinase inhibitors, the evolution of cancer treatment and particularly of surgery is likely to accelerate . As the efficacy of these new treatment options becomes clearer, some excisional procedures will likely become less common, while primary debulking procedures, now rarely done for cancers other than ovarian cancer, may become more frequent as these newer systemic treatments are able to mop up ‘residual disease’.…”

The significance of microscopic mass spectrometry with high resolution in the visualisation of drug distribution

“…A large body of clinical evidence has revealed that neoadjuvant chemotherapy is useful for a variety of solid tumours. The tissue excised during surgery or endoscopic biopsy can be used to investigate drug distribution56. Thus, a convenient method for evaluating the distribution of clinically used native (non-radiolabeled or non-chemically modified) drugs is urgently required.…”

Improving outcomes in gastrointestinal cancer

“…Genomics is widely employed, and proteomic and metabolomic information that impacts directly on diagnosis and management seems inevitable. No review issue would be complete without consideration of the current situation 6 . Most current targeted therapies focus on growth inhibitors, and, although admittedly the results are as yet modest, this should not detract from the principles that are being learned -again perhaps the analogy with breast cancer might be drawn.…”