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SUMMARY:One old and one new metabolic target to treat ovarian and breast c
 ancer - Dr Alan Richardson\, Pharmacology Lead and Group Lead of Cancer re
 search group
DTSTART:20220303T160000Z
DTEND:20220303T170000Z
UID:TALK170570@talks.cam.ac.uk
CONTACT:Kirsty Shepherd
DESCRIPTION:Despite recent advances\, ovarian cancer remains an inadequate
 ly treated disease with only 40% of patients surviving more than 5 years w
 ith advanced disease. Rather than developing new drugs to treat this disea
 se\, an alternative is to repurpose existing drugs that are normally used 
 to treat diseases other than cancer. A large body of preclinical research 
 has suggested that statins\, drugs normally used to treat elevated cholest
 erol\, should be effective anti-cancer agents. However\, this has not been
  borne out in numerous clinical trials. In the first part of this seminar\
 , I will argue that this is because the clinical trials have not been desi
 gned with due regard to preclinical data and that the failure of statins a
 s anti-cancer therapeutics in patients to date reflects\, at least in part
 \, a lack of diligent clinical trial design. Importantly\, the data that w
 ill be presented will point to how statins might be used effectively to tr
 eat cancer\, including cancers such as pancreatic cancer that are dependen
 t on K-Ras.\n\n \n\nIn the second part of the seminar\, I will present the
  results of a screen to identify genes which contribute to the resistance 
 to the chemotherapeutic agents to treat ovarian cancer. One hit from this 
 screen unexpectedly is involved in regulating branched-chain amino acid (B
 CAA) metabolism\, a biological process not previously implicated in drug r
 esistance. Inhibition of branched-chain keto-acid dehydrogenase kinase (BC
 KDK) stimulates BCAA metabolism and sensitizes both ovarian and breast can
 cer cells to paclitaxel. The reduced BCAA levels inhibit the mTORC1-Aurora
  signalling axis which regulates microtubule function during cell division
 . Considering that paclitaxel also impairs microtubule function\, this sug
 gests a mechanistic basis for the synergy between BCKDK inhibitors and pac
 litaxel. Considering that some cancers are dependant on BCAA metabolism\, 
 these data suggest that improved inhibitors of BCKDK may be useful as eith
 er single agents or in combination with chemotherapy to treat cancer.
LOCATION:https://eng-cam.zoom.us/j/89897561076?pwd=YTFSa28xSG1Tdy9zRjlPQno
 wZ3BEQT09
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