Project Description
CYP450 Enzyme Inhibitors as Novel Palliative Care Analgesics in Oral Cancer
Pain due to cancer is
notoriously difficult to treat, adds substantially to the emotional burden of
having cancer, and is more frequently observed with certain tumors, such as
oral squamous cell carcinomas (OSCC). Pain
due to oral cancer afflicts ~60% patients awaiting treatment and even 20% of
treated patients continue to report significant pain. However, available analgesic treatments for
oral cancer pain are often limited in efficacy and are associated with adverse
side effects or rapid tolerance. Thus, there is a critical need for novel
analgesics to treat pain in oral cancer patients. Because pain is often the first symptom of
oral cancer, occurring even when the tumor is still quite small in size, it is
likely that OSCC cells control the activities of surrounding sensory pain nerve
terminals (nociceptors) at the site of the tumor. It is known that nerve
terminals in the oral cavity express pain-sensing channels that when activated,
leads to the stimulation of the pain pathway. We have shown that certain lipids
released from human oral cancer cells contribute to pain-like behavior in
rodents. It has been shown that synthesis
of many of these lipids in the cell can be controlled by activity of a class of
enzymes such as cytochrome P450 (CYPs). We therefore speculate that inhibiting
the activity of these CYP enzymes can block the production of these lipids, in
turn blocking oral cancer pain. Therefore, in a pilot study, we will evaluate
the potential effect of five FDA-approved CYP inhibitors on -active lipids
released from oral cancer cells. Use of FDA-approved drugs in our study will
maximize clinical implication as they are already approved for humans. There
are several such CYP inhibitors used for various disease conditions in the
clinic. However, none have been explored for their role in cancer pain.
We believe that the
potential impact and innovation of the research approach is extraordinary, from
both scientific and medical perspectives, since the studies address a novel
mechanism for cancer pain and, the results will promote future research aimed at
developing drugs that treat cancer pain at the site of tumor development as
well as at studying the mechanisms of cancer pain at a cellular level.
From the
perspective of palliative care, the location of OSCCs (i.e. mouth, tongue and
pharynx) offers a unique opportunity to formulate these FDA-approved drugs as a
mouthwash, with trans-mucosal delivery of the CYP inhibitors directly to the
tumor site. This local delivery of medicine
would offer a unique opportunity to help control oral cancer pain and would
hopefully improve the quality of life of these cancer patients.
Bio
Shivani Ruparel, PhD is an
Assistant Professor at University of Texas Health Science Center at San Antonio. Her primary focus of research is studying
mechanisms of cancer pain. She has been focusing on differences between mechanisms by which cancers that cause pain at the primary
site of tumor development and cancers that causes pain only upon bone metastasis.
Her current research interest lies in determining ways oral cancer cells
mediates pain at the site of tumor development and interactions by which tumor
cells mediate activities of peripheral nociceptors. Additionally, her research
also includes testing novel analgesics for oral cancer pain in the intent to
improve quality of life of cancer patients.
Email: RuparelS@uthscsa.edu