Tumors
Abnormal sections of tissue in the body are called tumors or neoplasms. Some tumors are benign (not normally dangerous) and some are malignant (e.g. composed at least partly of cancer cells). Occasional benign tumors are diagnosed as pre-cancerous if the doctor has good reason to believe cancer will develop.
Lymphomas and leukemias are cancers in the body’s fluids. The malignant cells are mixed in with the healthy ones. Myelomas are cancers of the bone marrow. Sarcomas and carcinomas are cancers in solid organs and referred to as solid tumors. More than 80 percent of tumors are solid tumors.
Tumors in solid cancers change as they get larger. The very small ones, including microscopic tumors that cannot normally be detected, are clumps of cells with no dedicated supporting blood vessels. This is called the avascular phase of growth. Oxygen and nutrients for the cells travel by diffusion.
The capacity for diffusion transport is low. Tumors can grow to about 1 to 2 cubic millimeters before the cells start running low on nutrients. The body must produce new blood vessels to feed the cancer cells. The growth of new blood vessels is called angiogenesis.
The body makes new blood vessels all the time – whenever a person puts on weight and his or her belly expands, or whenever a papercut heals, angiogenesis is happening. Scientists have explored the mechanics of this process, and it is very complex. The body produces chemical signals to start (Tumor Angiogenesis Factor) and stop blood vessel growth. Chemicals that stop blood vessel growth are called angiogenesis inhibitors.
There are over a hundred types of cancer and among the differences are tumor growth rates – some very fast and some slow to the point of almost being benign. Within a tumor can be both malignant and non-malignant cells. And there is even more heterogeneity. Malignant cells in the tumor can have different biological characteristics (morphological and phenotypes). This heterogeneity, and the fact that cancer cells mutate faster than healthy cells, are key to the resilience of cancer and why so many cases of cancer develop resistance to chemotherapy treatment.
Cancerous cells are different from healthy cells. For one thing, they tend to be less specialized. They are still recognizable as being of the type from which organ they developed – skin cells or liver cells, etc. But they are less fully specialized, and indeed bear a relationship to healthy cells similar to children and adults. Malignant cells don’t respond to the body’s signals to stop dividing and to undergo cell death. This is why you see cancer cells described as immortal. It’s part of what makes cancer so tenacious and so difficult to fight medically. Benign tumors are more controlled in their growth than malignant ones. Cells in malignant tumors grow rapidly in an uncontrolled manner.
Tumor burden is the number of malignant cells in the tumor. Cancers with a low tumor burden are usually more responsive to chemotherapy because they have a higher proportion of cells that are multiplying than larger tumors. The growth factor of a tumor refers to the percentage of cells multiplying at any point in time.
The Microenvironment
Cells in the body are surrounded by extracellular fluid and other cells. They communicate more with and are influenced more by nearby cells than they are by other cells in the body. The characteristics of the fluid – including pH, salinity, presence of dissolved oxygen and minerals and hormones – influence the cells and are influenced by the cells. Cancer cells affect healthy cells in their vicinity. And when tumors grow, they affect the circulatory system and induce growth of new blood vessels. The creation of new blood vessels – a process called angiogenesis – is necessary whenever a human body grows. When children grow up there is a lot of angiogenesis happening. When a person gains adipose tissue – love handles for instance – new blood vessels form to serve the new cells. The blood vessels bring oxygen and nutrients to the new tissue and carry off waste products. Tumors are no different from healthy tissue in this respect. When a cancer tumor grows, blood vessels grow inside it.
Larger tumors are referred to as being in the vascular phase. Angiogenesis eventually accomplishes the transition of tumors from small and relatively benign to the invasive and malignant vascular phase, Once blood vessel networks form, the tumor can grow large. Vascular phase tumors are more invasive and metastasis happens after the tumor has reached this stage. Local invasion is the term for growth of the tumor and crowding out of nearby tissue. It can produce pain and other medical consequence. Metastasis involves spread of the cancer to other parts of the body, but this is through the birth and growth of new tumors, not an extension of the original tumor.
Hallmarks
Douglas Hannahan and Robert Weinberg have proposed six “hallmarks of cancer”
http://www.cell.com/cell/fulltext/S0092-8674(11)00127-9
These more precisely explain the tendency of cancer to grow uncontrolled and to resist the body’s attempts to shut it down. The hallmarks are widely accepted by the oncology community.
- self-sufficiency in growth signals
- insensitivity to antigrowth signals
- angiogenesis
- invasion of tissue and metastasis
- unlimited replicative potential
- evasion of apoptosis
Heterogeneity and Adaptability
Physiologists who look deep into tumors tell us they are heterogeneous. This has been known for some time, but recent detailed cell-by-cell sequencing reveals even more diversity than scientists had previously suspected. There can be multiple phenotypes. The structure of blood vessels within a tumor is usually more complex than it is in healthy tissue, and there can be changes in the tissue density within the tumor. Further, the immediate environment around each cell shapes its characteristics. The immediate fluid pressure outside a cell can vary inside the tumor, and there can be variations in oxygen levels in the blood and intercellular fluid. If drugs are administered, there will be variations in drug levels, too.
This environment actually encourages the development of tumor resistance, as treatments that kill a majority of cells leave a few alive that multiply. Scientist think that the resistance is due to both genetic mutations and expressions of genes.
Some, but not all, cells in a tumor exhibit Warburg-effect metabolism. Glycolysis is a series of biochemical reactions that breaks down glucose to pyruvate. Cancer cells undergo glycolysis at a rate 200 times higher than normal cells. This is called the Warburg Effect. Unless there is a shortage of oxygen, this is a less efficient method of metabolism, but it is a distinguishing characteristic of (some) cancer cells that investigators are interested in possibly exploiting in a treatment scheme.
Etymology
The ancient Greek physician and philosopher Galen used the word oncos (which means swelling) —of tumors. That’s where we get the word oncology from (oncology is the study of cancer.) Hippocrates, an even older Greek, applied the word carcinoma to cancer. This word (carcinoma) is today applied to one sort of cancer. The symbol for the astrological sign Cancer is a crab. It is speculated Hippocrates applied the word for crab to cancer because the tumor’s branching network of blood vessels looked like the multilegged creature.
Grading tumors
Upon diagnosis, a tumor may be assigned a grade, which is not the same as the stage of the cancer. Oncologists have special grading systems for some types of cancer; it there is no specific system for a cancer, the generic system of G1 (least abnormal) to G4 (most abnormal) can be employed. Non-malignant cells tend to be specialized for the tissue they are in. Cancer cells are less specialized. A tumor mass that looks more like normal tissue under a microscope is called well-differentiated and can be classified a G1, while undifferentiated tissue of mature cancer is classified as G4.
Metastasis
Metastasis is the spread of a cancer beyond the organ it started in. The cancer is said to metastasize. Metastasis is a scary word in the oncology world. About 90 percent of cancer deaths occur after metastasis. If a cancer metastasizes, the prognosis for the patient takes a downturn. A main goal in cancer treatment is to prevent growth to a point where metastasis occurs. The situation is often so dire the goal of treatment shifts to palliation.
Metastasis happens when cancer cells break from the original tumor and lodges in another organ. The type of cell is the same as the first organ. So when lung cancer metastasizes to the bone and brain, the cancer cells in the bones and brain are actually lung cells. When prostate cancer metastasizes, the malignant cells in other organs can be identified as prostate cells.
Metastatic cancer is also called distant stage cancer or diffuse or disseminated cancer. There is not a continuous trail of malignant cells from the first tumor to other tumors in the body. Instead, malignant cells seem to travel through the body’s transportation system. Solid tumors become metastatic through the epithelial to mesenchymal transition (EMT).
The lymph system and the circulatory system carry cancerous cells and are a vector for metastasis. Tumor cells often get trapped in a lymph node, and lymph nodes are a common place where metastatic cancer shows up. Tumor cells in the bloodstream can get stuck in a capillary and grow into the adjacent organ. Fluid-filled cavities are also conduits for cancer to metastasize. The place or origin is called the primary tumor and the distant one might be called a secondary cancer. Small outposts of malignant cells can function as “sanctuary” sites for the cancer. The malignant disease sometimes survives at those sites when treatment attacks the primary tumor.
Growth Rates for Common Cancers
Tumors grow exponentially, as seen in the exponential, Gompertz and universal law models. The rate of growth depends on the size of the tumor. One way to describe the growth rate is in terms of doubling time, or the time it takes for the population of cells – and tumor volume – to increase by 100 percent.
There is a lack of clinical data at non-symptomatic stages, but it can be assumed that two to three decades can elapse between the first carcinogenic stimulus and the emergence of the neoplasm in many cancer. A person who gets a sunburn or smokes cigarettes in his 20s may not have a detectable tumor for years, but the cancer is slowly growing. Typical doubling times for a tumor range from 60 days for very aggressive tumors to 100 days for non-aggressive tumors.