Speculative fractal explanation
James Fleck, MD, PhD: Anticancerweb 07(09), 2021
The fractal pattern is present throughout nature. These two leopards may not be exactly alike, but self-similarity leads to immediate species identification. In fact, the leopard skin pattern is fractal, a rough or fragmented geometric shape that can be divided into parts, each of which is a reduced-size copy of the whole, as defined by Benoît Mandelbrot. In 1980, the mathematician moved to IBM, where he used complex numbers and quadratic polynomials to build an infinite iteration image. This image, known as Mandelbrot set, was the first to reproduce in an electronic system the fractal geometry found in nature. Fractal geometry is defined by multiple levels of organization, irregular shapes and self-similarity. Transposed to biological models, this phenotypic expression is present in both health and disease. Tumor cells have fractal expression, which allows the identification of specific patterns used in pathological diagnosis. Let’s take lung adenocarcinoma as an experimental model. Tumor heterogeneity was identified in light microscopy in former described five histologic subtypes (lepidic, acinar, papillary, micropapillary and solid). Each subtype is an iteration image making possible specific morphologic diagnosis.
Since the beginning of the 21st century, an incipient tumor molecular expression was described in most solid tumors. In 2014, the Lung Cancer Mutation Consortium brought together 20 institutions in the US and identified driver mutations in 62% of lung adenocarcinoma. Patients who expressed a driver mutation and were treated with biological targeted drugs had a median survival of 3.5 years. Patients who expressed a driver mutation who did not receive biological targeted therapy had a median survival of 2.4 years. The median survival decreased even further (2.1 years) in those patients who did not express any driver mutation and were not treated with targeted therapy. Therefore, the identification of a driver mutation became a parameter of quality of care in the treatment of lung cancer.Currently, several driver mutations have been described in lung adenocarcinoma, creating genomic patterns, whose molecular spatial geometry has not yet been entirely identified. The figure represents nine driver mutations found in lung adenocarcinoma, showing their respective percentage of expression.
Each specific molecular phenotypes described in lung adenocarcinoma, is an actionable mutation and has been used to turn off addictive oncogenic cell behavior. The table below describe some therapeutic options for advanced lung adenocarcinoma according its molecular phenotype. Grade of recommendation varies according the evidence-based already provided in clinical trial.
References:
1. Benoît Mandelbrot: The Fractal Geometry of Nature, 1983
2. Lung Cancer Mutation Consortium, 2014: https://www.lungcancerresearchfoundation.org/research/lung-cancer-mutation-consortium/
3. Ian Stewart: Mathematics of Life: Unlocking the Secrets of Existence, Profile Books, 368p, London, 2012
The use of biological targeted drugs has been revolutionary to cancer tratment adding more median survival rate to deseases with high mortality. If we think about the driver mutations in lung adenocarcinoma, whose molecular spatial geometry has not yet been entirely identified, there is a large unknown territory to explore and evolve from. In the future we will be able to increase significantlly life span and life quality of the cancer pacient.
Technology is a great ally of medical sciences, and the possibility of a personalized intervention for the patient is a great bet for gains in future treatments, which demonstrates that investment in studies in this area of research is essential. A new discovery in this area may revolutionize other sectors or, as in the case of the article above, generate gains and better therapeutic results for lung adenocarcinoma.
It's amazing how medicine is getting advanced every day for the possibility of better, more effective and personalized treatments, through technological advances. It is yet another advance that can lead to better treatment results and better prognosis.
The usage of our current knowledge about patterns of geometric-spatial presentation of mutations is extremely relevant, as it allows patients to have ,once the fractal pattern has been identified, a more targeted and consequently more effective treatment.
What an interesting phenomenon. In Medicine, often the most trivial observations lead to some of the greater breakthroughs in clinical care, akin to how the observation of greater and bizarre angiogenesis near tumors by various historical physicians (particularly Rudolf Virchow and Edwin Goldmann) led years later to Judah Folkman's research team developing the first anti-angiogenic drugs, still used to this day. Perhaps, the fractal pattern of adenocarcinoma is a mere consequence of the processes behind its carcinogenesis we have yet to uncover. I wonder if this fractality of lung carcinomas might lead humanity down a similar path.
Please login to write your comment.
If you do not have an account at Anticancerweb Portal, register now.