For decades, cancer has been viewed as a biological enemy. What if we've been wrong all along?
For centuries, tumors have been viewed as unqualified biological villains—rogue cellular processes that destroy lives without purpose. But what if certain tumors actually played a constructive role in shaping the diversity of life? This revolutionary perspective comes from carcino-evo-devo, a theory proposing that hereditary tumors have served as evolutionary innovation engines throughout the history of multicellular life.
Developed primarily by Andrei P. Kozlov and his colleagues, this theory suggests that benign, hereditary tumors provided the raw cellular materials necessary for evolutionary breakthroughs. They may have offered extra cell masses where evolutionarily novel genes could be expressed, potentially leading to the emergence of new cell types, tissues, and organs 3 .
This theory connects three fundamental biological processes: cancer (neoplastic development), evolution (evo), and individual development (devo). By examining their interconnection, carcino-evo-devo aims to explain previously puzzling biological phenomena and potentially become a unifying biological framework 3 6 .
The carcino-evo-devo theory challenges conventional wisdom by proposing that hereditary tumors have contributed to progressive evolution. The central hypothesis, termed "evolution by tumor neofunctionalization," posits that tumors provided developing organisms with additional cellular real estate where evolutionary innovations could emerge 3 .
This perspective doesn't suggest that malignant, lethal cancers provide evolutionary advantages. Rather, it focuses on benign tumors or those at early developmental stages that don't kill their hosts but provide cellular material where evolutionary experimentation can occur 3 .
A fundamental question in evolutionary biology has long been: How do genetic innovations find expression in physical form during evolution? Traditional evolutionary theory explains how existing traits are selected, but has struggled to fully account for the origin of completely novel structures like the brain, liver, or complex sensory organs.
Carcino-evo-devo proposes a solution: tumors may provide the necessary cellular playgrounds where new genes can be expressed without disrupting existing functions. These additional cell masses serve as evolutionary test beds where nature can experiment with new genetic combinations 3 .
A compelling theory must generate testable predictions, and carcino-evo-devo has done exactly this. One of its most significant predictions involves what Kozlov's team terms TSEEN genes—Tumor-Specific, Evolutionarily-New genes 1 .
If tumors indeed provide cellular material for expressing evolutionarily novel genes, then we should find genes that are:
Kozlov's laboratory embarked on a series of investigations to identify and characterize such genes 1 3 6 :
One compelling example is the PBOV1 gene, discovered to be a human-specific gene with virtually no expression in normal adult tissues but significant expression in various cancers, including breast, prostate, and ovarian cancers 6 .
| Tissue Type | Gene Expression Level | Significance |
|---|---|---|
| Normal breast tissue | Undetectable | Baseline control |
| Breast cancer | High | Confirms tumor-specific expression |
| Normal prostate tissue | Undetectable | Baseline control |
| Prostate cancer | Moderate to High | Supports tumor-specificity pattern |
| Various other normal adult tissues | Undetectable to Minimal | Reinforces evolutionary novelty hypothesis |
| Gene Name | Evolutionary Status | Expression Pattern | Implications |
|---|---|---|---|
| BRACHYURY (T) | Evolutionarily conserved | High in tumors, low in normal tissues | Ancient genes can show TSEEN pattern |
| HS.633957 cluster | Evolutionarily new | Predominantly in tumors | Supports the core prediction |
| Multiple other TSEEN genes | Evolutionarily new | Various human cancers | Pattern holds across gene families |
To conduct this pioneering research, scientists required specialized biological materials and methodological approaches:
| Research Tool | Primary Function | Examples from Studies |
|---|---|---|
| Tumor Biobanks | Provide diverse tissue samples for comparison | Collections of various human cancer and normal tissues |
| Genomic Databases | Identify evolutionarily novel genes | Human genome databases, comparative genomic tools |
| Gene Expression Assays | Measure where and when genes are active | PCR, microarrays, RNA sequencing |
| Animal Models | Study tumor processes in evolutionary context | Goldfish with hyperplastic head growths |
| Bioinformatics Tools | Analyze evolutionary relationships between genes | Phylogenetic analysis software, sequence alignment programs |
Computational approaches to identify evolutionary patterns in tumor genomics
Techniques to measure gene expression across different tissue types
Frameworks to understand how tumors might contribute to evolutionary change
The carcino-evo-devo theory reaches beyond basic biological research, offering fresh perspectives on several scientific fronts:
This theory doesn't seek to replace established evolutionary models but rather to complement them. It offers explanations for phenomena that other theories struggle to fully account for, particularly the rapid emergence of evolutionary novelties 1 6 .
The theory emerges alongside other critical reevaluations of cancer biology. Recent technological advances, particularly in genome sequencing, have revealed paradoxes challenging the orthodox "cancer as a genetic disease" paradigm .
While primarily an evolutionary theory, carcino-evo-devo may eventually influence medical approaches. The discovery of TSEEN genes opens possibilities for new therapeutic targets and diagnostic approaches 1 3 . Understanding the deep evolutionary connections between development and cancer may provide fresh perspectives on cancer prevention and treatment.
The carcino-evo-devo theory represents a paradigm shift in how we view both cancer and evolutionary processes. By suggesting that tumors have played a role in life's creative diversification, it challenges deeply entrenched views of cancer as an unqualified biological evil.
Though the theory continues to develop and requires further validation, it has already generated confirmed predictions and provided plausible explanations for previously mysterious biological phenomena. It reminds us that in science, seemingly settled questions—like the fundamental nature of cancer—can contain hidden depths waiting to be explored.
For further exploration: The four-part series "Theory of the Evolutionary Role of Hereditary Tumors (Carcino-Evo-Devo): History of Development and Current State" was published in Biology Bulletin Reviews throughout 2024.