Add-on Onvansertib Overcomes Resistan... - Advanced Prostate...

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Add-on Onvansertib Overcomes Resistance to Zytiga in mCRPC, Early Data Show

JLS1 profile image
JLS1
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This came out a few days ago and I don't see anyone else posted it yet. I don't subscribe to Prostate Cancer News Today so I can't access the whole article. Perhaps someone else here does subscribe?

prostatecancernewstoday.com...

Add-on Onvansertib Overcomes Resistance to Zytiga in mCRPC, Early Data Show

Sep 04, 2019 01:03 pm | Jose Marques Lopes, PhD

Onvansertib Adding the investigational oral therapy onvansertib to a regimen of Zytiga (abiraterone acetate) and prednisone overcomes resistance to Zytiga in men with metastatic castration-resistant prostate cancer (mCRPC), according to early results of a Phase 2 clinical trial. The study (NCT03414034) is testing whether a once-daily dose of Trovagene’s onvansertib is beneficial in adults with mCRPC […]

-and here's a link to more info on Onvansertib. A bit confusing, so I won't attempt to"'translate":

trovageneoncology.com/onvan...

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bloomberg.com/press-release...

NPfisherman profile image
NPfisherman

Saw this about a week ago....another promising candidate to the arsenal...Other drugs are further along through Phase 2 and headed towards Phase 3 that will be available sooner...new classes of drugs that will be "add-ons" to Zytiga, Xtandi, Erleada. There is HOPE because the Science is Comng !!!!

Thanks for posting the Science ....

All the best....

Don Pescado

AlanLawrenson profile image
AlanLawrenson in reply toNPfisherman

Do you care to list the drug candidates 'ahead' of onvansertib?

NPfisherman profile image
NPfisherman in reply toAlanLawrenson

Is this your post?

healthunlocked.com/advanced...

You write books on PCa--alternative and SOC treatments--I am sure you have that list already...

Don Pescado

NPfisherman profile image
NPfisherman in reply toAlanLawrenson

Is this you?

goodreads.com/author/show/1...

If you have looked all over 4 continents, then I am sure my list would look paltry compared to yours.... You should post a list.. Alan G Lawrenson...

Don Pescado

j-o-h-n profile image
j-o-h-n in reply toNPfisherman

Here he is (free plug):

amazon.com/ABC-Prostate-Can...

youtube.com/watch?v=MDBTpxx...

P.S. I'm still recovering from my penis reduction operation....j-o-h-n that is...

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 09/10/2019 6:20 PM DST

NPfisherman profile image
NPfisherman in reply toj-o-h-n

Dolly said size don't matter.... Do she and Anna get along well??

Fish

j-o-h-n profile image
j-o-h-n in reply toNPfisherman

Ana doesn't know about Dolly👀..... Dolly says size does matter... the smaller the better.... Hence reduction....

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 09/10/2019 7:06 PM DST

AlanLawrenson profile image
AlanLawrenson in reply toNPfisherman

Hi Don

Thanks for your posts. I am writing a 3rd Ed book on PCa. In fact, I essentially completed its 459 pages yesterday. I cover all SOC, but do look closely at future developments. Thus my asking for input. The new book covers 20 odd future therapies. Some will fall by the wayside, but others will become mainstream SOC over the next 1-5 years.

My brother's live has been saved by Lu-177 PSMA. Its still experimental everywhere. Why do men all have to do SOC and possibly die?

NPfisherman profile image
NPfisherman in reply toAlanLawrenson

Alan G Lawrenson,

Why do men all have to do SOC and possibly die?

I don't know as I have never endorsed SOC by itself.... I did SBRT to my one lesion found by Axumin scan and took heat from the person with the largest following here that claims SBRT will be proven to not be effective in oligometastatic PCa...

Since you have a list of 20 odd future therapies, then please post your list ....

In return, I will reply with the name of a drug that will be a game changer for MCRPC... Along with the name, will be evidence of why this drug is important and a case study showing it's ability to control MCRPC.

By posting your list, I can compare it to your future book....and feel comfortable that you are indeed, Alan G Lawrenson.... I am amazed that Darryl does not have you involved with the newsletter that he will be putting out, but perhaps, there is someone else involved with that issue.

I look forward to your reply with the list, and in return, I will be posting the information that I listed.

Don Pescado

AlanLawrenson profile image
AlanLawrenson in reply toNPfisherman

Future Developments

- I list a mini-extract only for the first 10 therapies only

1.Immune Cell Banking

Transplanting immune cells from healthy donors to people with cancer.

2.ProscaVax Vaccine

ProscaVax (Prostate-specific antigen (PSA) / Interleukin-2 (IL-2) / Granulocyte-macrophage colony-stimulating factor (GM-CSF)),

3.Ribosome-Targeting Drugs

A promising new treatment is a combination of two drugs that inhibits protein production by ribosomes. PCa work follows breast and blood cancer clinical trials being done now.

4.Machine Learning combined with Flow Cytometry to identify High Risk Prostate Cancer

Predicts the risk of either having an aggressive form of prostate cancer or lower grade PCa/BPH based upon the flow cytometry immune-phenotyping of myeloid-derived suppressor cells (MDSCs) and lymphocyte cell.

5.Computer Mutational Analysis Detects High Grade Prostate Cancer

Simply explained: Use cancer patient data to develop a computer model that can differentiate between aggressive and non-aggressive disease in early stage patients.

6.Natural Killer Cells activation by Chimeric Antigen Receptors

Use cutting-edge genome engineering technology, to develop methods to generate Chimeric Antigen Receptor (CAR) Natural Killer (NK) cells from NK cells in the blood.

7.Cell Senescence – Putting Cancer Cells to Sleep

The gene for KAT6A is the 12th most frequently amplified gene in cancer cells. Shutting down KAT6 stops cancer cells dividing, which Voss and Thomas call ‘putting them to sleep’.

8.An Integrated Stress Response Inhibitor

“We have discovered the molecular restraints that let cancer cells keep their ‘addiction’ under control and showed that if we remove these restraints, they quickly burn out under the pressure of their own greed for protein."

9.Starpharma’s Dendrimer Technology

Extract only: Starpharma’s underlying technology is built around dendrimers - a type of synthetic nanoscale polymer that is highly regular in size and structure and well-suited to pharmaceutical and medical uses. Starpharma has two core development programs, with one applicable to solid tumours. Starpharma has two internal DEP® products – DEP® docetaxel and DEP® cabazitaxel - in clinical trials with patients with solid tumours. Starpharma’s DEP® drug delivery platform has demonstrated reproducible pre-clinical benefits across multiple internal and partnered DEP® programs, including improved efficacy, safety and survival. By joining the drug to a dendrimer construct, very large increases in drug solubility have been achieved, which can enhance the ‘bioavailability’ of the drug.

This technology will change the efficacy of almost all cancer drugs in my opinion.

Disclosure: I am a shareholder of this stock.

10.Chimeric Antigen Receptor T-Cell Therapy (CAR-T)

CAR-T technology will be successfully applied in clinical prostate cancer therapy in the near future, but only with men with appropriate physiology (DNA genes, etc.).

I list the Title only for the other ‘therapies’ discussed in detail in my new book.

11.Protein Degrader ARV-110 enters Phase 1 clinical trial

12.First Patient dosed in a Phase 2 study with LiPlaCis (Cisplatin)

13.ProstAtak® Immunotherapy in Men undergoing Active Surveillance

14.Topsalysin Phase 3 trial approved for Intermediate Risk Localised PCa

15.Progenics AZEDRA: Hope for men with Neuroendocrine Tumours?

16.Mitochondrial-based Therapeutic Strategies for Eradicating CSCs

17.Zinc Therapy

18.

Mitochondrial Inhibitors

19.Bi-specific Antibody Therapy

20.EZH2 inhibitors

21.Calibr CCW702 Immunotherapy for mCRPC

22.Veyonda® Enhances Radiotherapy in PCa Treatment

.

Hopefully, the 460 page book “An ABC of Prostate Cancer Today – 3rd Edition” will be available from Amazon before the end of October (in eBook or print format).

By the way, I am happy to list these future developments, but am NOT interested in having a dialogue with ANYONE about any of them.

NPfisherman profile image
NPfisherman in reply toAlanLawrenson

Fair enough, I will give you two drugs, not one--

ZEN 3694-- a BRD4 inhibitor--There appears to be activation of HULLK --the driver of PCa tumorigenesis by BRD4 and p300...see below:

molecular-cancer.biomedcent...

ZEN 3694 is completing Phase 2 this fall...

clinicaltrials.gov/ct2/show...

In a case study done using the 2 drug combo using CURATE AI to determine dosing--a patient had their MCRPC regress without using maximum dosing...below:

onlinelibrary.wiley.com/doi...

But what about p300? Is there no answer? ....There is

CCS 1477--a p300 inhibitor, in clinical trials in the UK--

ascopubs.org/doi/abs/10.120...

They are a little over a year in on the study:

clinicaltrials.gov/ct2/show...

A recent ASCO poster--please note the diagram showing Enzalutamide and CCS1477 tumor suppression

cellcentric.com/media/uploa...

The question is can these 2 drugs be given together? I don't know, but they will be "add ons" to Abiraterone, Enzalutamide, Apalutamide, etc... The use of combination therapies, as done in HIV, will buy time and add to OS....a chronic disease state...

Thank you for your reply, Alan G Lawrenson... Like you, I am interested in the Science and also KAT 6A inhibitors which can "put cancers to sleep"... As I always say, "The Science is Coming !!!"

Don Pescado

JLS1 profile image
JLS1 in reply toNPfisherman

Thank you Don and Alan for posting this valuable and encouraging information!!

Are any of these treatments better/safer for someone , like my husband, who is in bone marrow failure after 4 Xofigo treatments? ( prior to Xofigo he was on Lynparza + Zytiga for almost 1-1/2 years, then Zytiga + dexamethasone & Xgeva along with the Xofigo). So many drugs I look at list low blood counts as a possible side effect. He's now on 4mg Dexamethasone + Darolutamide since early Feb. Hard to tell if it's working - PSA and alk phos have improved, slightly, but if it's determined to not be helpful, we need to have a backup plan FAST.

Tall_Allen profile image
Tall_Allen

biospace.com/article/releas...

JLS1 profile image
JLS1 in reply toTall_Allen

Thank you!!

Sxrxrnr1 profile image
Sxrxrnr1

I do subscribe, read this several days ago with great interest, having failed Xtandi and now prescribed Darolutamide which I have not received yet.

Have been on Indomethacin for 6 weeks seeking a backdoor resistance reset. Been unable to obtain Niclosamide,,however aware of trial at UC Davis as another reset option.

Have had a AR-V7 test which fortunately scored negative which suggests some optimism that Darolutamide may perform.

JLS1 profile image
JLS1

This came out again last Monday:

Onvansertib Helps Overcome Resistance to Zytiga in mCRPC Patients, Interim Phase 2 Data Show

DECEMBER 9, 2019

prostatecancernewstoday.com...

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