Personalising treatments: lessons from history

Stephan Tanneberger, Guest editor

Fifty years ago, when I was just starting out in cancer medicine, our team at the cancer centre attached to Berlin’s Academy of Sciences began our attempts to individualise chemotherapy treatments. We knew that response to different drugs varied enormously between patients, so we invented the ‘oncobiogram’ to try to select, in advance, the best treatment for each one. Modelled on the ‘antibiogram’ for selecting antibiotics, we cultivated biopsies (cell culture/organ culture), which we then treated with the different drugs in vitro. We evaluated the efficacy of this selection procedure in clinical trials, and the results were encouraging.

Less encouraging was what we learnt about the extreme heterogeneity of tumours in space and time. Our collection of more than a thousand of these cultures of human tumours showed individuality with respect to detailed histology, mitotic index, DNA synthesis, drug sensitivity and more. In a programme that spanned ten years, we realised then that the existence of a single ‘cancer state-specific cell defect’ is nothing more than a scientific illusion.

‘Personalised’ or ‘precision’ medicine is often seen as a purely 21st century concept that is just in its infancy. A better understanding of the historic context could help inform more realistic expectations about what it will be able to deliver.

The annual rate of publications on cancer chemotherapy doubled between 1997 and 2014, alongside an expansion in expensive new anticancer drugs. But the reported results do not show convincing clinical progress. Given the biological diversity and continuing evolution of tumours, it is perhaps not surprising that patients cannot be cured using a single targeted therapy. Even today’s sophisticated technologies still give us only a snapshot of the dynamic carcinogenic process.

Cancer is an error of cell division induced by avoidable carcinogens or unavoidable body aging. It is an inherent part of our biology. Targeted treatment remains a concept continually pursued, rather than realised, and realistically speaking, we may never see a definitive breakthrough.

Yes, the immune system is intriguing and a new generation of immune checkpoint inhibitors hold interesting potential. However, it has not evolved to eliminate tumours, but rather to control ‘minimal deviations’ of cell division at the start of carcinogenesis. There are other interesting approaches that also need to be explored, and in a time of great dreams of cancer therapeutics, we should not forget cancer prevention.

Oncology does need personalised medicine. But a renewed focus on the patient, their needs and feelings, must be central to that personalisation. Our patients, many of whom are old, may have other needs more important than access to highly sophisticated drugs.
My plea, particularly to the new generation of colleagues, is: when you look at someone’s tumour to understand its driver mutations, don’t forget to also look in their eyes, understand the person, and ‘personalise’ that human being in the room with you. This we call eubiosia – a ‘good life’, a human right for all, including those of us suffering from cancer.

Stephan Tanneberger was Director of the Central Institute of Cancer Research of the Academy of Sciences of the German Democratic Republic from 1974 until 1990. He spent much of his later career with the Bologna-based Associazione Nazionale Tumori, developing their local and international work supporting home-based palliative care services. h.s.tanneberger (at) gmx.de

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