The circulatory system, composed of the heart, blood vessels, and blood, transports oxygen and nutrients while removing waste. Cancer, both in its development and through treatments, significantly disrupts the normal function of this system. The interaction between malignant cells and blood circulation affects the body’s ability to grow, repair, and defend itself. This impact ranges from physically altering the structure of blood vessels to changing the composition of the blood itself.
Fueling Growth: Tumor-Driven Blood Vessel Formation
A growing tumor mass quickly outstrips its initial blood supply, leading to a state of low oxygen known as hypoxia. This lack of oxygen acts as a powerful signal, forcing the tumor to engage the circulatory system by inducing the formation of new blood vessels from pre-existing ones, a process called angiogenesis. The tumor releases chemical signals, most notably Vascular Endothelial Growth Factor (VEGF), which bind to receptors on nearby healthy endothelial cells.
This signaling causes endothelial cells to proliferate and migrate, sprouting new capillaries that grow toward the malignant mass to bring in the necessary oxygen and glucose. The new vasculature created within the tumor is often structurally abnormal, lacking the organized layers and tight junctions found in healthy vessels. These tumor vessels are characteristically leaky, disorganized, and tortuous, leading to inefficient blood flow and further contributing to the hypoxic tumor environment.
The abnormal permeability of these vessels allows plasma proteins and fluid to leak out, increasing the pressure within the tumor tissue. This increased pressure can physically impair the delivery of therapeutic drugs, making treatment less effective. The very network built by the tumor to sustain its growth also provides a convenient pathway for cancer cells to escape into the wider circulation.
The Pathway for Spread: Metastasis via Blood Vessels
The circulatory system acts as the primary highway for metastasis, the process by which cancer cells travel from the primary tumor to establish secondary growths in distant organs. Before they can travel, cancer cells must first invade surrounding tissue and enter the bloodstream, a step known as intravasation. The leaky, disorganized nature of the tumor vasculature makes it easier for these cells to breach the vessel wall and gain access to the circulation.
Once in the bloodstream, these cells, now referred to as circulating tumor cells, face immense challenges, including the mechanical stress of blood flow and attack from the body’s immune cells. To survive, cancer cells often travel in clusters or cloak themselves by associating with platelets, offering them a protective shield.
The final step in this journey is extravasation, where the circulating tumor cells exit the vessel to colonize a new site. They typically lodge in small capillaries and then adhere to the endothelial lining before actively moving through the vessel wall into the surrounding tissue. This complex, multi-step process is successfully executed by only a small fraction of cells that enter the blood, but it is what turns a localized disease into a systemic one.
Changes in Blood Components
Cancer profoundly alters the composition of the blood, leading to several systemic complications. One of the most common is anemia, a reduction in the number of red blood cells or the amount of hemoglobin, resulting in fatigue and weakness. Cancer-related anemia is frequently caused by the chronic inflammation associated with the disease, as inflammatory cytokines interfere with iron utilization and suppress the bone marrow’s ability to produce new red blood cells.
Another significant alteration is hypercoagulation, or an increased tendency for the blood to clot, which manifests as venous thromboembolism. This complication is often referred to as Trousseau Syndrome, and it is particularly common in patients with certain cancers like those of the pancreas, stomach, and lung. Malignant cells can release pro-clotting factors, such as Tissue Factor, which initiates the coagulation cascade even without a vessel injury.
Cancer and its treatment can affect the bone marrow where all blood cells are produced, leading to myelosuppression. This suppression can result in low counts of white blood cells (neutropenia), which compromises the immune system and increases the risk of serious infection. Similarly, a decrease in platelets (thrombocytopenia) can impair the body’s ability to clot, leading to easy bruising or internal bleeding.
Damage to Heart and Vessels
The heart and major blood vessels are often subject to damage, particularly from cancer therapy. The term cardiotoxicity describes direct injury to the heart muscle caused by certain chemotherapy agents, most notably anthracyclines, which can lead to conditions like cardiomyopathy or heart failure. This type of damage can occur acutely during treatment or years later, requiring long-term monitoring for survivors.
Radiation therapy directed at the chest for cancers like breast or lung cancer can also inflict structural damage on the heart and surrounding vessels. Exposure to radiation can accelerate the hardening and narrowing of the arteries (atherosclerosis) and cause inflammation of the heart’s lining or valves. This effect is often delayed, with cardiovascular problems sometimes appearing a decade or more after the initial treatment.
In rare instances, a large tumor mass located near the heart or a major vessel can cause direct physical impairment. For example, a tumor in the mediastinum can physically compress the superior vena cava, a major vein returning blood to the heart, which severely impedes circulation. Whether from the direct mass effect of the disease or the side effects of life-saving treatments, the physical integrity of the circulatory system is frequently compromised.