Registration for a live webinar on 'Neuroleptic malignant syndrome' is now open.
See webinar detailsWe noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
Printable Handouts
Navigable Slide Index
- Introduction
- Prostate cancer (PCa): drug resistance paradigm
- Androgen receptor (AR) & hormone sensitive PCa
- AR in hormone resistant PCa
- Development of CRPC
- Challenge in identifying cancer drug targets
- Phenotypic screening
- CDK inhibitor p27 as a tumor suppressor
- SKP2 targets p27 for degradation
- SKP2 overexpression in human cancers
- Inverse correlation between p27 & SKP2 in PCa
- Complex regulation of p27
- SKP2 overexpression downregulates p27 in PCa
- Screen for inhibitors of p27 downregulation in Pac
- SMIP004 downregulates SKP2
- SMIP004-induced inhibition of CDK2 activity
- SMIP004-induced cell cycle arrest
- SMIP004-induced apoptosis/cytotoxicity
- SMIP004 inhibits PCa cell growth in soft agar
- SMIP004 inhibits growth of LNCaP xenografts
- Cellular pathways induced by SMIP004
- Pathways regulated by SMIP004: UPR
- SMIP004 & the unfolded protein response (UPR)
- UPR signaling
- Pathways regulated by SMIP004: G1/S & Rb
- Effect of SMIP004 on cyclin D1 & Rb
- Pathways regulated by SMIP004: AR signaling
- SMIP004 downregulates AR protein
- Cellular pathways affected by SMIP004
- SMIP004 rapidly induces anabolic pathways
- Upregulation of the electron transfer chain (ETC)
- Mitochondrial respiration & ATP production
- ETC complexes
- SMIP004 causes oxidative stress
- Cellular pathways induced by SMIP004
- OXPHOS inhibition potential in cancer therapy
- Publications; respiration essential for cancer cells
- Comparison of selected genes: Zhan myeloma
- Comparison of selected genes: Brune lymphoma
- Comparison of selected genes: Shai brain
- Comparison of selected genes: Dyrskjot bladder
- Comparison of selected genes: Wei lung
- Varying metabolic phenotypes of cancers
- Large heterogeneous tumor
- Responses of heterogeneous tumor
- Questions remaining
Topics Covered
- Drug resistance in prostate cancer
- Role of androgen receptor in prostate cancer
- Difficulties in finding new prostate cancer drug targets
- Rational behind screening for p27 downregulators
- Potential for OXPHOS inhibitors in cancer therapy
- SMIP004: p27 downregulator and potential drug
Talk Citation
Wolf, D. (2017, August 31). Mitochondrial inhibition as a novel therapeutic approach in drug-resistant cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 11, 2024, from https://doi.org/10.69645/KMAD6032.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Dieter Wolf has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Mitochondrial inhibition as a novel therapeutic approach in drug-resistant cancer
Published on August 31, 2017
31 min
A selection of talks on Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is Dr. Dieter Wolf.
I'm a professor in the Tumor Initiation and Maintenance
Program at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California.
I also hold an appointment in the school of
Pharmaceutical Sciences of Xiamen University in China.
This lecture is going to be about
"Mitochondrial Inhibition as a Novel Therapeutic Approach in Drug-Resistant Cancer".
Drug resistance is one of the major problems in cancer therapy.
0:28
While scientists and physicians avail of plenty
of drugs that kill cancer cells often in a selective manner,
typically tumors develop resistance to these drugs relatively quickly.
In our studies, we have addressed prostate cancer as a paradigm of drug resistance.
Prostate cancer is the most common male malignancy
and the second most common cause of death from cancer in men.
There are approximately 250,000 new cases diagnosed each year.
And there are over two million patients living in the US with numbers increasing steadily.
Due to the large number of patients,
the prostate cancer drug market is huge and has
doubled from 8 to 16 billion US dollars in the past five years.
The main problem with prostate cancer comes when the standard of care drugs stop working.
This is when the disease progresses to drug resistance,
or so called castration resistant prostate cancer or CRPC.
So as the naming is saying,
1:33
castration resistant prostate cancer is
resistant to a form of therapy that is known as castration.
Castration aims at the withdrawal of male sex hormone or androgen.
And it can be achieved in a number of ways including
surgical orchiectomy or chemical castration using a series of drugs.
Now let me explain why castration also known
as androgen deprivation is a therapy for prostate cancer.
It has been well-established for decades,
that the androgen receptor or AR which is bound and activated by
androgens is the main oncogenic driver in hormone-sensitive prostate cancer.
AR activation leads to growth and survival signals that spur cancer growth.
Conversely, androgen locate through ADT,
or androgen deprivation therapy has
profound therapeutic benefit by stopping
the growth and promoting the death of prostate cancer cells.
Two main approaches are used in ADT of hormone-sensitive prostate cancer,
removing androgen from the circulation and secondly,
AR blockers or anti-androgens.
The situation is somewhat different in castration resistant prostate cancer,
Hide