Media Releases

An end to cancer pain?: U of T researcher finds the “pain trigger”

April 23, 2015

TORONTO, ON. – A new study led by Uni­ver­si­ty of Toron­to researcher Dr. David Lam has dis­cov­ered the trig­ger behind the most severe forms of can­cer pain. Released in top jour­nal Pain this month, the study points to TMPRSS2 as the cul­prit: a gene that is also respon­si­ble for some of the most aggres­sive forms of andro­gen-fuelled can­cers.

Head of Oral and Max­illo­fa­cial Surgery at the Fac­ul­ty of Den­tistry, Lam’s research ini­tial­ly focused on can­cers of the head and neck, which affect more than 550,000 peo­ple world­wide each year. Stud­ies have shown that these types of can­cers are the most painful, with suf­fer­ers expe­ri­enc­ing pain that is imme­di­ate and local­ized, while pain treat­ment options are lim­it­ed to opi­oid-fam­i­ly phar­ma­ceu­ti­cals such as mor­phine.

It was while con­duct­ing clin­i­cal research at the Uni­ver­si­ty of Cal­i­for­nia San Fran­cis­co, though, that Lam noticed some­thing inter­est­ing. A major­i­ty of head and neck can­cer patients are men – lead­ing him to inves­ti­gate a genet­ic mark­er with a known cor­re­la­tion to prostate can­cer, TMPRSS2.

“Prostate can­cer research already knows that if you have the TMPRSS2 gene mark­er, the prostate can­cer is much more aggres­sive. They’ve also shown that this is andro­gen (male hor­mone) sen­si­tive.”

In his study, Lam, who is joint­ly appoint­ed as a Con­sul­tant Sur­geon at the Princess Mar­garet Can­cer Cen­tre and a Clin­i­cian at the Mount Sinai Wass­er Pain Man­age­ment Cen­tre, ascer­tained that TMPRSS2 was not only present in patients suf­fer­ing from head and neck can­cers – it was also preva­lent in much greater quan­ti­ties than in prostate can­cer.

But was there a link to pain?

Vis­i­ble on the sur­face of the can­cer cells, TMPRSS2 comes into con­tact with the body’s nerve pain recep­tors, which then trig­gers the pain. Lam was also able to deter­mine a clear, cor­rel­a­tive rela­tion­ship between the two: the more TMPRSS2 that comes into con­tact with nerve pain recep­tors, the greater pain is pro­voked.

Lam and his fel­low researchers fol­lowed up this obser­va­tion by look­ing at dif­fer­ent types of can­cers with known pain asso­ci­a­tions – for instance, cer­tain breast and melanoma cell lines. These cells were grown and labelled for the TMPRSS2 genet­ic mark­er.

Accord­ing to clin­i­cal data, head and neck can­cer is the most painful form of can­cer, fol­lowed by prostate can­cer, while melanoma, or skin can­cer, sits at the bot­tom of the pain scale.

But what sur­prised the researchers was that the pres­ence and amount of TMPRSS2 in these can­cer cell cul­tures stood in exact cor­re­la­tion with the known lev­el of pain each can­cer caus­es.

“It was exact­ly what we know clin­i­cal­ly about pain asso­ci­a­tion,” adds Lam.

A New Direc­tion for Drug Research

The star­tling dis­cov­ery of TMPRSS2’s role in trig­ger­ing can­cer pain may lead to the cre­ation of tar­get­ed can­cer pain ther­a­pies that effec­tive­ly shut down the expres­sion of this gene or its abil­i­ty to infil­trate pain recep­tors in the body.


Dr. Bri­an Schmidt, Pro­fes­sor at New York Uni­ver­si­ty Col­lege of Den­tistry, Direc­tor of the Blue­stone Cen­ter for Clin­i­cal Research and a co-author of the study states, “The dis­cov­ery that TMPRSS2 dri­ves can­cer pain demon­strates anoth­er way that can­cers lead to suf­fer­ing. Inhi­bi­tion of its activ­i­ty in patients might pro­vide a new form of treat­ment for can­cer pain.”

“Any can­cer that is painful before ini­ti­at­ing drug treat­ment – we can label the can­cer cells for TMPRSS2 and look for this par­tic­u­lar mark­er,” explains Lam, who adds that the most effec­tive approach to end­ing pain would be to tar­get the pro­duc­tion and expres­sion of the pain gene.

But there may be oth­er ram­i­fi­ca­tions to the TMPRSS2 study: fur­ther research may yet uncov­er what role the increased expres­sion of TMPRSS2 plays in the aggres­sive­ness and mor­bid­i­ty rates asso­ci­at­ed with cer­tain aggres­sive can­cers – and whether or not shut­ting down the pain gene will have any oth­er ben­e­fi­cial side effects than reduc­ing dis­com­fort.

The study also involved researchers from New York Uni­ver­si­ty and the Forsyth Insti­tute (Cam­bridge).


Com­bin­ing the rigours of bio­log­i­cal and clin­i­cal research with a supe­ri­or edu­ca­tion­al expe­ri­ence across a full range of under­grad­u­ate and grad­u­ate pro­grams – with and with­out advanced spe­cial­ty train­ing – the Fac­ul­ty of Den­tistry at the Uni­ver­si­ty of Toron­to has earned an inter­na­tion­al rep­u­ta­tion as a pre­mier den­tal research and train­ing facil­i­ty in Cana­da. From the cut­ting-edge sci­ence of bio­ma­te­ri­als and micro­bi­ol­o­gy, to next-gen­er­a­tion nanopar­ti­cle and stem cell ther­a­pies, to ground-break­ing pop­u­la­tion and access-to-care stud­ies, the mis­sion of the Fac­ul­ty of Den­tistry is to shape the future of den­tistry and pro­mote opti­mal health by striv­ing for integri­ty and excel­lence in all aspects of research, edu­ca­tion and clin­i­cal prac­tice.


Media Con­tact:

Erin Vol­lick, Com­mu­ni­ca­tions Offi­cer
T: 416–979-4900 ext. 4381