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.  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 and stop blood vessel growth.  Chemicals that stop blood vessel growth are called angiogenesis inhibitors.

Larger tumors are referred to as being in the 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.

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 cell mutate faster than healthy cells are key to the resilience of cancer and why so many cases of cancer develop resistance to chemotherapy treatment.

Traditional chemotherapy drugs are cytotoxic – they kill cells.  In the 1990s a new approach to cancer treatment was formulated.  The idea was to stop the cancer by stopping tumor growth, and stopping tumor growth by stopping the growth of new blood vessels.  By giving the patient angiogenesis inhibitors – either identical to the chemicals the body naturally produces for that purpose or other chemicals that inhibit generation of blood vessels – the oncologist can stop the cancer in its tracks,  This new paradigm was called anti-angiogenesis therapy or angiogenesis inhibition therapy.  It caused a great deal of excitement in the medical community. That excitement has faded as angiogenesis inhibition results in clinical practice were less than revolutionary.  However, several angiogenesis inhibitors have been approved by the FDA as cancer drugs and they are in use today.

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 times, but recent detailed cell-by-cell sequencing  reveals even more diversity than scientists had been suspected.    Further, the immediate environment around each cell shapes its characteristics.  Within a tumor are variations in oxygen levels in the blood and 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.

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.

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.