Week 7 Flashcards
Cancer cell characteristics
- Have mutations and often abnormal nuclei that are enlarged. May have an abnormal number of chromosomes (aneuploidy)
- Arise from dividing (mitotic) cells and generally have an
unlimited ability to divide (immortal) - Can typically divide without growth factors (auto-stimulate)
- Appear dedifferentiated (though they often retain some characteristics of cell & tissue origin) and do not contribute to body functioning
- Form tumors
- Migrate and invade new tissues: malignant
- Solid tumors can spur angiogenesis
- Migrate via the bloodstream/lymph to colonize new tissues: metastasis (distant organs)
- Become abnormal gradually through a multistage process, not dissimilar from evolution
Metstasis diagram
Blood cell development interrupted
Tumor incidence and growth increases with time
-risk factors: smoking, radiation -> mutation, body can’t tolerate over time
-multistep process takes years, decdes, risk factor increases w/ age, more common in older adults
Causes of cancer
Genetics (small amt ~ 5%)
– Inherited, predisposing alleles for individuals to develop cancer
* Present in the germ cells: germline mutations (from beginning as baby)
– Plus new somatic mutations
* Means that the germline does not pass on the cancer. It will only possibly pass on the predisposition (accumultes over time)
– All evidence indicates that more than one mutation is needed
- Environmental – the preventable aspect
– carcinogens (agents that cause cancer)
– New or acquired alterations in cell behavior - Somatic cells and germ cells
– Environmental factors may make cells/body more susceptible to cancer cell survival as well as acting as mutagens (agents that cause mutations) - Radiation
– e.g. UV light and ionizing radiation cause DNA damage - Chemicals
– tobacco smoke, pollutants, pesticides and more, contain known mutagens
– some chemicals are also suspected of promoting cell growth - Viruses
– e.g. Hepatitis B & C viruses can cause liver cancer
Cancer Treatment
- Surgery to remove small, localized tumors (not reached basal lamina/vessel)
- Kill the more rapidly dividing cells which are found in tumors
– Chemotherapy, Radiation therapy
– Naturally, this method has some inherent toxicity to normal dividing
cells, especially the highly active stem cells in tissues – e.g. bone marrow HSC
– Afterwards, these individuals will often need bone marrow or hematopoietic stem cell transplant - Need to kill cancer cells specifically
– Need for specific information on the unique features of the cancer cells vs. normal cells
– Need for specific targeting of drug to the cancer cell vs. normal cell
– There are only a handful of these – e.g. Gleevec
– Immunotherapy, which relies on driving immune recognition of unusual, unique cancer cells, is starting to yield some good results - CAR T-Cell Therapy
Leukemia
-Cancer of a WBC
-Sooner/earlier than myeloma or lymphoma which are caused by mutation later in differentiation stages
-not RBC bc no nucelus/DNA for cancer
- ALL: acute lymphoblastic leukemias
- CLL: chronic lymphocytic leukemias
- AML: acute myelogenous/myeloid leukemias
- CML: chronic myelogenous/myeloid
leukemias - Categorization schemes:
– Pathological pattern (histology, morphology)
– Acute or chronic dynamics
– Antibody gene rearrangement stage
– Cell surface markers
– Treatment responses - Leukemias, like many cancers, are characterized by overproliferation of non-functional cells that take over tissues, first of which is to take over blood functions
The Atomic Bomb and Leukemia
Incidence in Japan
bomb inceased rates of leukemia through radiation exposure (carcinogen) -> damages DNA -> cancer
Leukemia’s Many Effects
- Fatigue and malaise
- Appetite loss and weight loss
- Fever
- Anemia
- Bleeding, slow-healing cuts, and bruising
- Infections
- Bone or Joint pain
- can also have vomiting
Chronic Myelogenous Leukemia
- Many are a result of a chromosomal rearrangement known as a reciprocal translocation that happens between 2 specific chromosomes (9 and 22)
– Philadelphia chromosome (after Peter Nowell’s lab at U.Penn. and David Hungerford at Fox Chase Cancer Ctr.) -> uncontrolled cell division in myeloid cells - Produces a specific gene rearrangement,
a gene fusion (chimera) - Chimeric gene arising from t9;22 = BCR-ABL
- Fusion protein results with part of BCR and part of ABL
- BCR encodes a regulator of apoptosis, a cell death pathway
- ABL encodes a regulator of cell growth (ABL is a tyrosine kinase, an enzyme that phosphorylates other proteins, a modification that typically
activates the target protein) - The chimeric protein produced is a constitutively active kinase that constantly drives cell proliferation (fusion makes cell constantly active, no apoptosis)
Gleevec
- Gleevec (imatinib) is a drug specifically targeting the aberrant BCR-ABL protein for chronic myelogenous leukemia (CML)
-targeted treatment
-inhibits BCR-ABL gene, halts growth of cancer in CML patients - Gleevec is one of the few specific treatments
available - Each cancer is distinct and very often
heterogeneous within an individual
– Consider the variety of mutation possibilities and
the differences in cancer promoting & cancer
inhibiting activities in/on each body + drug resistant cancers - Difficult to find a single effective cure
