At the time of the follicular dendritic cell sarcoma discovery, information on the effect of chemotherapy and radiation on it was nonexistent.
The best physicians could do was try existing chemotherapeutic agents.
With no evidence of the clinical benefit of chemotherapy, many of the first cases were treated solely with complete resection and/or radiation.
However, 12 of 31 patients who had surgery alone as primary treatment relapsed.
Of the patients who received surgery and radiation, 2 of 8 relapsed.
It became apparent that better treatment options were necessary.
Being so similar to lymphomas, physicians began using a common leukemia and non-Hodgkin’s lymphoma chemotherapy regimen on FDCS patients: CHOP.

The CHOP regimen consists of Cyclophosphamide, Doxorubicin, Oncovin, and Prednisone (CHOP).
They all exploit different pathways common in cancer cells.
Cyclophosphamide slows or stops cell growth.
It targets cells that are rapidly dividing, which include cancer cells that are self-sufficient in growth signals and insensitive to antigrowth signals.
More importantly, the biological actions of cyclophosphamide are dose-dependent.
At high doses it is very cytotoxic; its metabolite phosphoromide adds an alkyl group to the N7 position on guanine resulting in arrested growth and cell death.
The metabolite is only formed in cells with low levels of cytoplasmic aldehyde dehydrogenase (ALDH), resulting in relatively low chemotherapeutic toxicity in other non-cancer cells like bone marrow.
It is also an immunosuppressant and decreases the inflammatory response.
At low doses, while it is less cytotoxic, it shows some anti-angiogenic properties.
The mechanism is not fully understood; it is thought that it interferes with the VEGF growth factors produced in and around the tumor microenvironment.

Doxorubicin interferes with cell growth and replication by intercalating in DNA.
This stops topoisomerase II from relaxing the DNA strands and inhibits transcription.
Recent studies have also shown that doxorubicin may be involved in the  PI3K/AKT/mTOR pathway.
An important hallmark of cancer, Akt is part of the cell survival pathways by inhibiting apoptosis.
There is also evidence that Akt is involved in angiogenesis and vascular maturation.
Activation of the PI3K/AKT/mTOR pathway mediates VEGF production in cells.
Therefore, doxorubicin has a dual role in cancer treatment: it inhibits cell survival (causes apoptosis), and decreases angiogenesis.

Oncovin, more commonly known as vincristine, is a mitotic inhibitor.
It binds to tubulin dimers, inhibiting the assembly of microtubule structures like the cytoskeleton and mitotic spindle.
Although this drug still cannot strictly target cancer cells, cancer cells have a higher average turnover of microtubules making them more susceptible to the cytotoxicity of oncovin.
Prednisone, the last drug in the CHOP combination therapy is a corticosteroid that acts as an immunosuppressant.

Although some results were seen in FDCS patients treated with CHOP, they were far from consistent.
Using a chemotherapy regimen designed for another cancer is an archaic “guess-and-check” way of treating a disease.
In 2008 the largest review of FDCS was published as a retrospective analysis on 98 patients and the authors recommended that surgery with no adjuvant treatment be the standard for FDCS treatment.
Patients treated with surgery alone had a recurrence rate of 40% and those treated with adjuvant therapy after surgery did not have a significantly different recurrence rate.
Radiation and/or chemotherapy had no significant effect in improving patients’ disease-free survival.
With developments in our understanding of the hallmarks of cancer, however, novel approaches to specifically targeting and treating FDCS are being developed.
At the time of the follicular dendritic cell sarcoma discovery, information on the effect of chemotherapy and radiation on it was nonexistent. The best physicians could do was try existing chemotherapeutic agents. With no evidence of the clinical benefit of chemotherapy, many of the first cases were treated solely with complete resection and/or radiation. However, 12 of 31 patients who had surgery alone as primary treatment relapsed. Of the patients who received surgery and radiation, 2 of 8 relapsed. It became apparent that better treatment options were necessary. Being so similar to lymphomas, physicians began using a common leukemia and non-Hodgkin’s lymphoma chemotherapy regimen on FDCS patients: CHOP.
The CHOP regimen consists of Cyclophosphamide, Doxorubicin, Oncovin, and Prednisone (CHOP). They all exploit different pathways common in cancer cells. Cyclophosphamide slows or stops cell growth. It targets cells that are rapidly dividing, which include cancer cells that are self-sufficient in growth signals and insensitive to antigrowth signals. More importantly, the biological actions of cyclophosphamide are dose-dependent. At high doses it is very cytotoxic; its metabolite phosphoromide adds an alkyl group to the N7 position on guanine resulting in arrested growth and cell death. The metabolite is only formed in cells with low levels of cytoplasmic aldehyde dehydrogenase (ALDH), resulting in relatively low chemotherapeutic toxicity in other non-cancer cells like bone marrow. It is also an immunosuppressant and decreases the inflammatory response. At low doses, while it is less cytotoxic, it shows some anti-angiogenic properties. The mechanism is not fully understood; it is thought that it interferes with the VEGF growth factors produced in and around the tumor microenvironment.
Doxorubicin interferes with cell growth and replication by intercalating in DNA. This stops topoisomerase II from relaxing the DNA strands and inhibits transcription. Recent studies have also shown that doxorubicin may be involved in the  PI3K/AKT/mTOR pathway. An important hallmark of cancer, Akt is part of the cell survival pathways by inhibiting apoptosis. There is also evidence that Akt is involved in angiogenesis and vascular maturation. Activation of the PI3K/AKT/mTOR pathway mediates VEGF production in cells. Therefore, doxorubicin has a dual role in cancer treatment: it inhibits cell survival (causes apoptosis), and decreases angiogenesis.
Oncovin, more commonly known as vincristine, is a mitotic inhibitor. It binds to tubulin dimers, inhibiting the assembly of microtubule structures like the cytoskeleton and mitotic spindle. Although this drug still cannot strictly target cancer cells, cancer cells have a higher average turnover of microtubules making them more susceptible to the cytotoxicity of oncovin. Prednisone, the last drug in the CHOP combination therapy is a corticosteroid that acts as an immunosuppressant.
Although some results were seen in FDCS patients treated with CHOP, they were far from consistent. Using a chemotherapy regimen designed for another cancer is an archaic “guess-and-check” way of treating a disease. In 2008 the largest review of FDCS was published as a retrospective analysis on 98 patients and the authors recommended that surgery with no adjuvant treatment be the standard for FDCS treatment. Patients treated with surgery alone had a recurrence rate of 40% and those treated with adjuvant therapy after surgery did not have a significantly different recurrence rate. Radiation and/or chemotherapy had no significant effect in improving patients’ disease-free survival. With developments in our understanding of the hallmarks of cancer, however, novel approaches to specifically targeting and treating FDCS are being developed.
Follicular dendritic cell sarcoma