Cancer: when our own cells become the enemy

Erin Martinez, Ph.D.Trevecca University

Physician Assistant ProgramSeptember 30, 2013

What is cancer?

= a malignant tumor

= abnormal cell mass that develops when cells grow too much

= cells that escape their normal surroundings, invading locally and travelling to distant locations

benign

Moving from normal tissue to cancer

Bastid J, Ciancia C, Puisieux A, Ansieau S . Role of TWIST proteins in cancer progression. Atlas Genet Cytogenet Oncol Haematol. December 2009 .

Normal cells

Benign tumor

Malignant tumor = CANCER

Basement membrane

Blood vessel

What does cancer look like?Breast cancer: normal to cancer

Ductal carcinoma in situ

DeNardo and Coussens Breast Cancer Research 2007 9:212

What does cancer look like?Colon cancer: normal to cancer

Normal

Tumor

Cancer

Rose and Wu. The Internet Journal of Pathology. 12:1. 2011

What does a cancer cell look like?The Hallmarks of Cancer

Cell Hanahan and Weinberg, 2000.

Hallmarks of Cancer: physiological changesKeeping the foot

on the gas of growth

No brakes on growth!

Cells don’t die easily

Cells get more blood supply

Cells divide forever, and

ever…

Cells escape and spread

1

23

4

65

Cell growth in cancer

• Hallmarks 1 and 2: Keeping the foot on the gas of growth and no brakes on growth!

• Progress though the cell cycle more quickly than a normal cell• Don’t follow normal rules for stopping the cell cycle (checkpoints)

http://eishinoguchi.com/checkpoint.htm

Cancer cells resist death

• Hallmark 3: Cells don’t die easily

• Things that can usually cause programmed cell death (apoptosis) – DNA and protein damage– lack of nutrition/oxygen– buildup of waste – lack of survival signals from other cells – death signals from other cells

• Cancer cells ignore these and survive!

Cancer cells are immortal

• Hallmark 4: cells divide forever, and ever…

• Normal cells stop growing or die when telomeres are gone

• Cancer cells activate telomerase or do abnormal kinds of DNA recombination to survive!

http://www.med.nyu.edu/skirball-lab/sfeirlab/Research.html

Cancer cells induce angiogenesis

http://www.cancer.gov/cancertopics/understandingcancer/angiogenesis/AllPages

• Hallmark 5: cells get more blood supply• Fast growing cells beginning to form a tumor need more

nutrients and need to get rid of more waste than local blood vessels can provide

• Promote formation of new blood vessels (angiogenesis) with signaling molecules (example: VEGF)

Cancer cells are on the move

• Hallmark 6: cells escape and spread

• Normal cells die when they loose contact with surrounding cells or the basement membrane

• Cancer cells gain ability to migrate locally and sometimes flow through bloodstream and grow in a distant site (metastasis)

Prostate cancer metastasis imaged

with PET

J Nucl Med February 2006 vol. 47 no. 2 287-297

How do normal cells become cancerous?

• Changes in gene expression and activity – most often caused by mutations

• Mutations = changes in DNA that alter expression or activity of the gene

• Two main types of genes with mutations in cancer:1) Oncogene – genes that normally promote growth are

mutated to be hyperactive2) Tumor suppressor – genes that normally inhibit growth

are mutated to be inactive

– It takes several genetic alterations to cause cancer

How do we fight cancer? • First surgery, then other therapies

• Target fast-growing cells- Radiation - Chemotherapy Kill all fast-growing cells - bad side effects

Other new cancer therapies

Targeted therapy to a oncogene in a tumor cellGleevec - inhibitor of oncogene in chronic myelogenous leukemia

Erbitux – inhibitor of oncogene in colorectal and head/neck cancerHerceptin - inhibitor of oncogene in breast cancer

Activating immune system against cancer cellsProvenge – activate man’s own immune cells against prostate cells

Anti-angiogenesis therapyAvastin – anti-VEGF antibody for metastatic colorectal cancer,

and advanced non-small cell lung cancer