The principles of natural selection also operate within the body, driving the progression of cancer. Tumors are not static masses of identical cells; they are dynamic and evolving populations. This internal evolution allows cancer to grow, spread, and develop resistance to treatments. Understanding a tumor as an evolving entity helps explain its complex nature.
The Genesis of a Tumor
A tumor’s evolution begins with a single cell in a process called initiation. This occurs when a normal cell acquires genetic mutations that disrupt controls on growth and division. These changes allow the cell to bypass the body’s regulations, breaking free from the cooperative community of healthy tissue.
These first mutations can be inherited, creating a predisposition to certain cancers. They can also be caused by environmental factors, like carcinogens in tobacco smoke or UV radiation. Many mutations are also the result of random errors when a cell copies its DNA. This initial genetic alteration provides the founding cell with a survival advantage, setting the stage for tumor development.
Clonal Selection and Tumor Diversity
After initiation, the altered cell divides, beginning a clonal expansion where a population of genetically identical cells grows. As this clone expands, new random mutations occur during cell division. This creates a branching pattern of evolution, where the original cell is the trunk and new mutations create branches, or subclones.
These subclones compete with each other and with normal cells for limited resources like oxygen, nutrients, and space. This competition creates selective pressure within the tumor’s microenvironment. Clones with mutations that help them access blood vessels or thrive in low-nutrient conditions will outcompete their rivals.
This process of mutation and cellular “survival of the fittest” results in tumor heterogeneity. A mature tumor is a complex ecosystem of many genetically distinct subclones. This internal diversity is what allows the cancer to progress and adapt, providing the raw material to evolve new capabilities like invading tissues or resisting therapies.
The Metastatic Cascade
Metastasis, the spread of cancer to distant organs, is a multi-step process requiring a specific set of acquired traits. It begins when a cancer cell detaches from the primary tumor and penetrates surrounding tissue, breaking through the natural barriers that contain it.
The cell must then invade a blood or lymphatic vessel, a process called intravasation. To survive transit through the circulatory system, cells must withstand mechanical stress and immune system attacks. The few that endure must then exit the bloodstream into a new organ in a step known as extravasation.
To establish a new tumor, the cell must thrive in a different organ environment, a process called colonization. This step is difficult because the new location may lack the necessary growth factors or cellular interactions. Each stage of metastasis acts as a selective filter, ensuring only cells with the right combination of traits can form a secondary tumor.
Genomic Tools for Tracking Evolution
Advanced genomic tools allow scientists to trace the evolutionary paths of tumors. The standard approach was a tissue biopsy, where a small tumor sample is removed and analyzed. A single biopsy provides only a static snapshot of one region, failing to capture the tumor’s full genetic diversity and potentially giving a misleading picture.
Next-generation sequencing (NGS) allows researchers to rapidly sequence the genetic code of cancer cells, creating a map of all mutations within a tumor. A more refined technique, single-cell sequencing, analyzes the DNA of individual cells. This identifies distinct subclones, reconstructs the tumor’s evolutionary tree, and helps scientists understand the dynamics between cell populations.
A liquid biopsy is another tool that analyzes circulating tumor DNA (ctDNA), which are fragments of DNA shed by cancer cells into the bloodstream. By taking a blood sample, doctors can detect and sequence ctDNA to monitor the tumor’s genetic changes over time. This provides a real-time view of the cancer’s evolution, particularly in response to treatment, without repeated surgical biopsies.
Implications for Cancer Therapy
Viewing cancer as an evolutionary process explains treatment resistance. When a patient receives therapy, the treatment may kill the dominant clone of cancer cells. This can cause the tumor to shrink, which appears to be a positive outcome.
If a rare subclone has a mutation that makes it resistant to the drug, it will survive. With its competitors eliminated, this resistant clone can multiply, repopulating the tumor with cells that are no longer affected by the therapy. This is natural selection occurring within the patient, leading to treatment failure.
This knowledge is leading to new therapeutic strategies like adaptive therapy, which aims to control the tumor rather than eradicate it. By using lower or intermittent drug doses, the goal is to maintain a population of drug-sensitive cells. These cells compete with resistant cells, helping to keep the resistant population in check and prolonging the treatment’s effectiveness.