Abstract

Simple SummaryTreatment of aggressive cancers often relies on chemotherapy. This treatment has improved survival rates, but while effective at killing cancer cells, inevitably it also kills or alters the function of others. While many of the known effects are transient and resolve after treatment, as survival rates increase, so does our understanding of the long-term health costs that accompany cancer survivors. Here we provide an overview of common long-term morbidities known to be caused by conventional chemotherapy, including the risk of relapse, but more importantly, the cost of quality of life experienced, especially by those who have cancer in early life. We aim to highlight the importance of the development of targeted therapies to replace the use of conventional chemotherapy, but also that of treating the patients along with the disease to enable not only longer but also healthier life after cancer.To prevent cancer cells replacing and outnumbering their functional somatic counterparts, the most effective solution is their removal. Classical treatments rely on surgical excision, chemical or physical damage to the cancer cells by conventional interventions such as chemo- and radiotherapy, to eliminate or reduce tumour burden. Cancer treatment has in the last two decades seen the advent of increasingly sophisticated therapeutic regimens aimed at selectively targeting cancer cells whilst sparing the remaining cells from severe loss of viability or function. These include small molecule inhibitors, monoclonal antibodies and a myriad of compounds that affect metabolism, angiogenesis or immunotherapy. Our increased knowledge of specific cancer types, stratified diagnoses, genetic and molecular profiling, and more refined treatment practices have improved overall survival in a significant number of patients. Increased survival, however, has also increased the incidence of associated challenges of chemotherapy-induced morbidity, with some pathologies developing several years after termination of treatment. Long-term care of cancer survivors must therefore become a focus in itself, such that along with prolonging life expectancy, treatments allow for improved quality of life.

Highlights

  • To prevent cancer cells replacing and outnumbering their functional somatic counterparts, the most effective solution is their removal

  • In spite of incontestable progress in the development and implementation of refined treatments, traditional chemotherapy, with cytotoxic agents continues to be the standard of care for many patients, including those diagnosed with leukaemia [1], lymphoma [2,3], breast [4,5,6], lung [7], and colorectal [8] cancers

  • After all, a fight to the cell death. Classic cytotoxins such as anthracyclines, platinum drugs or taxanes are extremely effective in eliminating cells with high proliferation rates, and as such, cancer cells are primary targets [1,9]

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Summary

Fight to the Death

In spite of incontestable progress in the development and implementation of refined treatments, traditional chemotherapy, with cytotoxic agents continues to be the standard of care for many patients, including those diagnosed with leukaemia [1], lymphoma [2,3], breast [4,5,6], lung [7], and colorectal [8] cancers. Aggressive cancers are those that proliferate fast, disseminate and resist treatment, and when cancer cells escape the subtle traps of highly specialised, targeted and refined interventionsƒ drastic measures, such as conventional chemotherapy, come into play. This review will focus on the off-target effects of conventional chemotherapy, and the implications of somatic cell adaptations to cancer fighting drugs

Relapse
Unintended Casualties
Tomorrow’s Problem
Findings
Conclusions
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