Cancer is defined by a common set of acquired capabilities that allow cells to grow and spread uncontrollably. While cancers originate in different organs, they all share functional traits known as the “hallmarks of cancer.” These hallmarks represent the physiological changes a normal cell must undergo to transform into a malignant tumor. Recognizing these shared traits provides a framework for understanding cancer progression and developing targeted therapies that interfere with the disease process.
Uncontrolled Proliferation
A fundamental characteristic of cancer cells is their ability to sustain their own growth signals, becoming independent of normal regulatory controls. Normal cells require external growth factors to bind to surface receptors before dividing. Cancer cells hijack this system by producing their own growth factors, creating a continuous self-stimulatory loop. They may also acquire mutations that permanently switch on growth factor receptors, sending a constant “go” signal to the cell’s internal machinery.
This abnormal signaling often involves proteins like the Ras family, which can become mutated and locked in an active state, driving relentless cell division. These genetic alterations grant the cell autonomy over its reproductive cycle.
Cancer cells must also ignore the signals that normally halt their growth. The cell cycle includes checkpoints that act as molecular “stop signs,” preventing division if DNA damage is detected. Cancer cells overcome these safeguards by inactivating tumor suppressor proteins, which function as the molecular brakes of the cell cycle.
For instance, the tumor suppressor protein p53 is frequently mutated or lost in over half of all human cancers, disabling a primary mechanism for stopping damaged cells from proliferating. The Retinoblastoma protein (Rb) is also often disabled, removing the restraint that prevents cell cycle progression. The combined effect of active growth signals and disabled growth-inhibitory controls results in the rampant, uncontrolled cell proliferation that defines a tumor mass.
Evasion of Cell Death and Immortality
Cells that acquire damage should trigger apoptosis, or programmed cell death, which is the body’s method for eliminating damaged cells without causing inflammation. Cancer cells develop strategies to resist this programmed suicide, ensuring their survival regardless of how abnormal they become. They may increase the production of anti-apoptotic proteins, such as those in the Bcl-2 family, which block the internal signals that initiate the cell death cascade.
This resistance to cell death is crucial for the persistence of the tumor, especially under the stress of therapeutic intervention. Evasion of programmed death is coupled with the acquisition of limitless replicative potential, often called cellular immortality.
Normal cells have a finite number of divisions governed by telomeres, structures at the ends of chromosomes that shorten with each division. Cancer cells overcome this limit by reactivating the enzyme telomerase, which rebuilds the telomere ends. Telomerase is active in about 90% of all human tumors, granting cancer cells an unlimited lifespan and the ability to accumulate necessary mutations.
Building a Resource Network
As a tumor grows, it requires a dedicated supply of oxygen and nutrients to support its rapidly dividing cell population. To meet this demand, cancer cells induce angiogenesis, the formation of new blood vessels from the pre-existing vasculature. Tumor cells secrete signaling molecules, such as Vascular Endothelial Growth Factor (VEGF), which prompts existing vessels to grow new capillaries directly into the tumor mass.
This vascular network delivers oxygen and glucose, removes waste, and provides a pathway for cancer cells to spread. Without this self-induced blood supply, tumors would remain dormant clusters of cells due to nutrient starvation.
Cancer cells also exhibit a distinct metabolic shift known as the Warburg effect, or deregulating cellular energetics. Unlike normal cells, which rely on efficient oxidative phosphorylation, cancer cells favor glycolysis. Glycolysis rapidly converts glucose into lactate, even when oxygen is plentiful.
This metabolic reprogramming provides a quick source of energy and generates intermediate molecules that serve as building blocks for new cellular components. This dual strategy of creating a new resource delivery system and optimizing resource utilization ensures the tumor’s sustained expansion.
The Ability to Spread
A tumor is designated as malignant when its cells acquire the ability to activate invasion and metastasis, establishing new colonies in distant parts of the body. Metastasis is a multi-step process that begins with cancer cells breaking down physical barriers. They shed anchoring molecules and secrete enzymes, such as matrix metalloproteinases, that degrade the surrounding tissue.
Once free, the cancer cells invade adjacent tissues and penetrate the walls of nearby blood or lymphatic vessels (intravasation). They travel through the circulatory system, surviving shear forces and immune surveillance.
At a distant site, the cells exit the circulation (extravasation) and migrate into the new tissue. The disseminated cells must then establish a new blood supply and begin proliferating, forming a secondary tumor.
This metastatic spread causes the majority of cancer-related mortality. Completing this cascade requires the cancer cell to be highly adaptable, surviving in vastly different biological environments from the primary site.
Genomic Instability and Immune Avoidance
The acquisition of these abnormal capabilities is accelerated by genomic instability and mutation, which acts as an enabling factor. Cancer cells exhibit defects in the machinery that maintains genetic integrity, such as DNA repair mechanisms. This instability leads to a significantly increased rate of mutations and chromosomal rearrangements. The resulting genetic chaos provides the raw material for rapid evolution, allowing the cell population to quickly acquire the specific mutations needed for other hallmarks.
Tumor-Promoting Inflammation
Genetic instability is often accompanied by tumor-promoting inflammation. Chronic inflammation in the tumor microenvironment releases growth factors and survival signals that remodel the tissue, facilitating invasion. Immune cells typically involved in fighting infection are co-opted to create a supportive, pro-tumor environment.
Evasion of Immune Destruction
Cancer cells must actively avoid immune destruction, circumventing the body’s natural defense system (immunosurveillance). Cancer cells develop mechanisms to hide from or suppress this response. They can downregulate the presentation of tumor-specific antigens, making themselves invisible to T-cells. They can also express immune checkpoint proteins, which act as “don’t attack me” signals to immune cells. The combination of genetic hyper-variability and active immune suppression allows the tumor to survive long-term.