Introduction

Cancer is a group of diseases characterized by uncontrolled and damaging proliferation of cells. Depending on the cell type that is exhibiting this uncontrolled proliferation, there are many types of cancers. For example, if the cells lining our skin becomes cancerous, it is called skin cancer. Similarly, if the cells of stomach lining become cancerous, it could be called stomach cancer and so on. Collectively, it is a very common condition with an estimated lifetime risk of getting any cancer as high as 1 in 2 for men and 1 in 3 for women1. Cancer is one of the leading causes of death throughout the world. It is likely that with advances in prevention, early detection and treatment, cancer becomes less fatal and more curable.

Normally, every living organism is made up of building blocks called cells. There are estimated 3.72 trillion cells in human body2. These cells are derived from the one cell formed at the time of conception, which multiply and differentiate into hundreds to thousands of varieties of cells such as liver cells, blood cells, nerve cells, bone cells etc. These varieties of cells organize themselves into various organs. Every organ in our body has cells that are specific to that organ. For example, liver cells or hepatocytes (liver), nerve cells (brain), chondrocytes (cartilage), various types of epithelial cells (lining of skin, hollow organs and glands) etc. In addition to organ specific cells noted above, each organ has additional non-organ specific such as cells lining blood vessels, blood cells, connective tissue cells, immune cells and other less common cells.

Cells and organs perform several normal functions throughout the lifespan. Cells may have to multiply for routine maintenance or as a response to injury and replace lost cells. Baseline need and capabilities for cellular multiplication vary depending on the type of cell, organ and other variables. Many normal cells have mechanisms to initiate cellular multiplication when needed. Some normal cells have constant need to multiply such as skin and other epithelial cells and bone marrow hematopoietic cells.

Under normal circumstances, cells have mechanisms to adjust their rate of multiplications to the needs of the body. Cells which have lost their normal function, irreversibly damaged or produced in excess may undergo cell death through regulated mechanisms such as apoptosis and are cleared from the body. Hence, normal cells multiply:

  • Only when needed.
  • Can slow down and stop when not needed.
  • Unwanted cells have mechanisms to undergo cell death (Ex. apoptosis).

Cells have complex mechanisms to accomplish these highly regulated processes.

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How cells become cancerous:

As noted above, cancer is characterized by uncontrolled proliferation of cells. This means, mechanisms controlling multiplication and cell death have been altered or damaged resulting in increased multiplication, decreased regulated cell death or both causing excessive accumulation of unwanted cells. Even though individual cells are microscopic, accumulation of hundreds of thousands to millions of abnormal cells may result in measurable tumor (lump).

A tumor could be benign or malignant (cancerous) depending on the ability of tumor cells to invade (invasion) and spread (metastases). A benign tumor does not have the ability to spread and are not cancers. A tumor is called a malignant tumor or cancer when the cells have the ability to invade or metastasize to other parts of the body.

Since genes and molecular mechanisms control cellular multiplication and cell death, alteration in genes, their expression, or other molecular alterations are key cellular mechanisms for initiating and maintaining malignant process. Excessive cellular multiplication occurs:

  • When cells gain ability to multiply when there is no need for them to multiply
  • When they lose their ability to recognize and stop multiplying
  • When they lose their mechanisms regulated cell death (such as apoptosis)

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What causes cancer:

Many conditions are known to result in or associated with cancer. Major known causes and predispositions include cigarette smoking, various chemical exposures, certain viral infections (such as HPV infection), inherited genetic conditions (such as BRCA mutations) and environmental factors (such as sun exposure, asbestos). Dietary factors and physical inactivity, certain medications (such as some chemotherapy) and many other associations exist. Many causes of cancer are yet to be identified. Cancers also occur as a result of random unpredictable mutations.

Known or unknown causes of cancer eventually results in deleterious mutations resulting in alteration of cellular mechanism resulting in malignant process. Since normal cellular mechanisms are many and complex, enormous varieties of alterations of the normal which could result in cancer exists.

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What is cancer staging:

Once a cancer is diagnosed, it is important to know the site of origin and extent of its spread. This is important both to assess prognosis and plan proper treatment. Staging is a process where various information is collected to understand the extent of cancer. AJCC (American Joint Committee on Cancer) TNM staging system is commonly used. Depending on tumor type, other staging system are also used (example, Ann Arbor staging system for lymphoma, risk stratification for leukemia etc.).

In TNM system, T stands for “tumor” (size and characteristics of primary tumor) N stands for “node” (if any spread to lymph glands) and M stands for “metastasis” (if any spread outside the primary tumor to distant parts of the body). Various T, N and M information is used collectively to derive a final stage. Final stage range from 0 to IV. Depending on the cancer type, these stages may be subdivided. Each cancer type has its own staging specifications. Hence T, N and M numbers and the final stage and its implications are not interchangeable between different cancer types.

Stage 0 (also called carcinoma in situ) means abnormal cancer cells are present which have not spread to nearby tissue or elsewhere. Stages I, II and III are cancers with increasing cancer burden and spread to lymph nodes. In stage IV, cancer has spread to distant parts of the body. While prognosis is better in earlier stages, it may be possible to treat cancer successfully irrespective of the final stage.

In addition to staging, additional information may help plan cancer treatment or assess prognosis. These additional information includes tumor grading (based on how abnormal tumor cells look under microscope), tumor genetic and molecular profile and other laboratory parameters.

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General treatment aspects:

Primary treatment:

With any cancer, when possible, treatment to achieve a cure is the first consideration. Since cancer process usually starts in one part of the body before it spreads, surgical removal or local forms of treatment (such as stereotactic radiation) are used to completely remove the tumor with adequate margins around the tumor. These general treatment aspects may not be applicable for blood/bone marrow cancers and some other cancers.

Neoadjuvant treatment:

Sometimes, some degree of tumor shrinkage or control may be needed prior to primary treatment to achieve better outcomes. Under these circumstances, treatments such as chemotherapy, medications or radiation etc. may be recommended prior to definitive surgery or other primary treatment modality. The treatment that is used prior to the primary treatment to facilitate primary treatment is called neoadjuvant treatment. Neoadjuvant treatment may be preferable in some early stage cancers based on tumor characteristics (such as triple negative or HER2 positive breast cancer).

Adjuvant treatment:

Since cancer cells are microscopic, potential spread to another body site is not always detectable or measurable with the available modalities such as scans. These potential microscopic spread to other body sites are reasons for theoretical risks of future recurrence. This risk of future recurrence vary depending on the cancer type, stage, genetic and molecular markers on the cancer cells and other factors.

If the theoretical risk of disease recurrence is considered significant, additional treatment may be used to reduce this future risk of recurrence and increase chances of cure. The treatment that is used after the primary treatment to reduce future risks of cancer recurrence is called adjuvant treatment. Chemotherapy or other medications, radiation or other treatment modalities may be used as adjuvant treatment depending on the cancer type and stage.

Other modalities:

Systemic treatment (such as chemotherapy, targeted therapy, monoclonal antibodies, immune based therapies etc.) can be used in advanced stages of disease and in some early stage cancer. These treatments may control disease, improve quality of life, prolong survival or in some cancers, achieve a cure. Many new medications and treatment modalities are being added to treat cancers.

Radiation therapy (various techniques) and other treatment modalities can be used either alone or in combination with systemic therapy to achieve local control, symptom management or achieve cure in some situations.

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Summary:

Cancer is an unwanted growth resulting from uncontrolled multiplication of cells which have the ability to invade and spread. Several known and many unknown causes result in cancer through multiple molecular mechanisms. Cancer is staged based on extent of disease. Several modalities of treatment can cure or control cancers. More and more new treatments are being added targeting many aspects of cancer.

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Cancer mechanisms and treatment targets

Slide One: Representation of a cell. Outer lining represents cell membrane. Inner circle represents nucleus with representative pair of chromosomes.