Liquid Biopsy For Cancer Metastasis Detections
Cancer metastasis is when the cancer cells spread from the primary tumor site to form new tumors in distant organs or tissues. It isn’t random as the cells spread to specific organ called organotropism. The cells that are spread are the same type(breast cancer cells spread to the brain but the cells are still breast cancer cells).
steps in metastatsis local invasion -EMT -Breakdown of basement membrane intravasation -entry into blood or lymp vessels -role of tumor-associated macrophages(TAMs) criculation -circulating tumor cells face immune attack and shear stress -often travel in clusters extravasion
how to detect metastasis usually through image such as CT scan, MRI etc The cells have to grow to a certain size before detecting.
Detect circulating Tumor cells -idea of the existence of CTCs was proposed long time ago -1990s-2000s:CTC detection re-emereged, eespecially with the development of enrichmentand detection platforms using nanotechnology In 2004, the cell search system(veridex) became the first FDA-cleared test for enumerating CTCs in metastatic breast, prostate, and colorectal cancers
What is in blood red blood cells are the most numerous with no nucleus (4.5-6 million per mL) White blood cells are fewer has a nucleus and is larger than the red blood cells(4,000-11,000 per mL) CTCs(if present in cancer patients) occur at <10 cells per mL of blood - extremely rare. It also has a nucleus. platelet(blood clotting) no nucleus cell fragments
how cell search works It is a blood test for enumerating circulating tumor cells. -Immunomagentic seperation using anti-EpCAM ferrofluids Ep-CAM is connected to a magentic end that is magnetically isolated -flourescence staining and identifications DAPI for nucleus(makes the nucleus blue) cytoskeleton (CK+) present in cells with epothilial origin CD45- if it is expressed it is usually a white blood cell
how does enumerating the number of CTCs help enrolled 177 mBC patients -patients with <5 CTC;s overall survuval is 21.9 months -patients with >5 CTCs have am overall survival of 10.9 months Kaplan-meyer plot -a statistical method to estimate the probability of an event occuring at different points in time -frequently used for clinical trials to observe treatments effectiveness
metastatic tumors are often hard to reach metastaic burden is dynamic, and liquid biopsy allows repreated sampling over time it provides a non-invasive snapshot of the tumor’s behavior
parsotix use microfluidic and cell deformability tumor cells are larger and less deformable than blood cells parsotix is better as cell search captures CTC’s using anti-EpCAM. Using anti-EpCAM is a limitation as some cancer types dont express EpCAM
ctDNA circulating tumor DNA: fragments from DNA released by tumor into blood stream the company focused on developed detection of ctDNA
liquid biopsy would allow: early detection of the cancer real time monitoring of tumor evolution
We created a Kaplan Meier graph on my jupyter notebook