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11.11.2014

Cialis Shown to Benefit Head and Neck Squamous Cell Cancer Patients

Researchers at the Sylvester Comprehensive Cancer Center, in collaboration with Johns Hopkins University, have found that Tadalafil, commonly known as Cialis, can be therapeutic for certain types of cancer. When used before surgery, Tadalafil can reduce certain cells that are detrimental to head and neck squamous cell carcinoma patients’ prognoses.

In a study recently published in Clinical Cancer Research, a publication of the American Association for Cancer Research, Donald T. Weed, M.D., professor of otolaryngology and Head and Neck Site Disease Group leader at Sylvester, and Paolo Serafini, Ph.D., assistant professor of microbiology and immunology, determined that moderate doses of Tadalafil given before surgery in patients with squamous cell cancers of the mouth and throat resulted in significant and potentially beneficial changes in the patients’ immune response to their cancer. The results suggest that the use of Tadalafil to modulate the body’s immune system could be a new therapeutic strategy for these cancers.

Head and neck squamous cell carcinoma is a deadly disease with a high rate of recurrence, despite advances in treatment. This is partly attributed to the fact that these cancers can suppress the body’s immune response to the abnormal tumor cells, allowing the cells to defend themselves against immune system attack. Two important components of this defense against immune attack are myeloid derived suppressor cells (MDSCs) and regulatory T cells (Treg).

MDSCs, named by Nature as one of the most important discoveries of the last decade, were originally identified at the University of Miami by Diana Lopez, Ph.D., professor of microbiology and immunology. They were then rediscovered and more fully characterized by Serafini and Vincenzo Bronte, M.D., at the University of Padova.

The presence of MDSCs and Treg at the tumor site or in the patient’s blood can negatively affect patient outcomes by quelling the immune response to the cancer. Preclinical studies showed that Phosphodiesterase-5 inhibitors, such as Tadalafil, could suppress MDSCs and Treg by modifying the tumor environment.

In a double-blind, placebo-controlled clinical trial, Weed and Serafini for the first time found that these preclinical findings hold true in humans. In addition, they discovered that Tadalafil increases CD8+T cells that boost immunity against squamous cells, resulting in minimized tumor growth.

“Specifically, a short course of daily Tadalafil treatment prior to surgery is sufficient to significantly reduce MDSCs and Treg systemically and at the tumor site,” said Weed. “It increases the percentage of tumor specific CD8+T cells in circulation and also promotes the activation of CD8+T cells at the tumor site.”

“What we are trying to do is prime the immune response,” said Serafini.

“The big picture message is that Tadalafil has an immune effect that is potentially therapeutic,” added Weed. “The whole idea is that throat cancers protect themselves from immune attack by recruiting MDSCs and Treg. Interventions like Tadalafil, which interrupt pathways for recruiting MDSCs and Treg, can restore the body’s immune response and enable a more efficient killing of the tumor.”

While both Weed and Serafini emphasize that the results of their trial do not support the use of Tadalafil alone as an option for cancer therapy, the researchers do hope that when combined with other immunotherapeutic strategies, the drug could reduce the tumor’s ability to defend itself against the immune system. To assess the viability of this theory, Weed and Serafini are now investigating whether Tadalafil can be combined with a tumor vaccine to cause an even more potent immune response and to reduce recurrence rates in patients with these cancers.

The two researchers are preparing to open a clinical trial and are collaborating with renowned cancer immunologist Olivera “Olja” Finn, Ph.D., at the University of Pittsburgh. Finn is the developer of the anti-MUC1 cancer vaccine, which is designed to prime the body’s immune response against an antigen (MUC1) commonly found on the surface of squamous cell carcinomas of the head and neck and other cancers. This trial will only be open at Sylvester, and it will enroll patients suffering from Stage 3 or 4 recurrence of squamous cell carcinoma of the head and neck who are undergoing surgery as treatment.

Patients will receive a short course of Tadalafil and the anti-MUC1 vaccine prior to surgery, then four courses after surgery. The goal is to demonstrate that this therapeutic strategy can effectively prime the body’s immune response against these cancers and hopefully reduce recurrence rates among patients. An added benefit is to promote a condition by which the body would recognize the cancer cells as foreign should they ever recur, even years after initial treatment, and the immune system would destroy them well before they could develop into a clinically significant tumor growth.

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