Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing

[Scout4answers]

pubmed.ncbi.nlm.nih.gov/352...

There must be more to this but can't figure out how to expand it.

Hisham F Bahmad 1, Timothy Demus 2, Maya M Moubarak 3 4, Darine Daher 5, Juan Carlos Alvarez Moreno 1, Francesca Polit 1, Olga Lopez 6, Ali Merhe 7, Wassim Abou-Kheir 3, Alan M Nieder 2 6, Robert Poppiti 1 6, Yumna Omarzai 1 6

Affiliations expand

PMID: 35225948 PMCID: PMC8883996 DOI: 10.3390/medsci10010015

Free PMC article

Abstract

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.

Keywords: CRPC; androgen-deprivation therapy; drug repurposing; prostate cancer.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1 Clinical diagnosis, patient stratification, and…

Figure 2

Figure 2 Drug repurposing in advanced prostate…

References

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These give launching points for research, trial research, MO discussions. Observational data, Petri dish data, and mouse data is just that. If I was a mouse, cool! If I were some cells in a Petri dish, double cool!

But good info for further investigation. Thanks.

[GoBucks]

ncbi.nlm.nih.gov/pmc/articl...

[Magnus1964 in reply to GoBucks]

Great article, thanks for sharing.

[Scout4answers]

Thanks guys

Good discussion of the candidates.

Conclusion:

Repurposing offers the advantage of bypassing Phase I and II clinical trials and, thus, speeds up drug approval. Many clinical trials have been designed that repurpose drugs to treat PCa, and more will follow. As electronic health records become more integrated, and artificial intelligence and precision medicine advance, more drugs will be strategically repurposed to treat PCa. Drugs that target the nuances of patient-specific tumors will be identified and hopefully improve patient life expectancy, cost of treatment, and quality of life. Functional genomics is also widely used to map cancer dependencies and identify therapeutic targets in cancer. This includes genetic screens based on CRISPR/Cas9 technology [69,70,71], reverse genetic screens, and chemogenomic screens [72]. In the era of personalized medicine, drug repurposing presents an opportunity and should be implicated, using computational genomic and proteomic technologies, to guide clinicians in their decision-making regarding patient treatment.

[cesces]

Did you ever wonder why these cancer cells are so adaptable and normal cells are so non-adaptable?

[Canoehead]

This is a great article, introducing many categories of drugs that may help us. But this also gets us into a very controversial area. The proponents of the metabolic theory, such as Jane McClelland, the Care Oncology people, and others have long advocated the use of repurposed drugs. These include, among others, Metformin, statins, various dewormers, and some old antibiotics. Additionally, on this site there has been extensive discussion of beta blockers, anti fungal and anti malarial.

Moving from there into what some might call conspiracy theory, the argument is that we will never know how good repurposed old drugs are because Phase 3 studies are very expensive and big Pharma makes too much money from their latest and greatest new drugs, (which extend life expectancy minimally) with costs in the thousands per month. Most of us long timers here know where we stand on this, and there is no point in poking the tiger with further discussion. That said, I’m a user (with my MO’s blessing) of Metformin and Atorvastatin, but I’m not ready for a dog dewormer.

[dhccpa in reply to Canoehead]

I use both a horse dewormer and a goat dewormer, and a statin, but have never used Metformin. I guess we all venture down different paths.

[Scout4answers]

Agreed , perhaps some European countries that have different criteria for testing will start trials for some of these off label drugs.I am on Atorvastatin and once my course of ADT is over I intend to take Berberine which I understand does the same thing as Metformin without any potential side effects.

[MateoBeach]

It is a rich mine of possible treasures. The challenge is finding the diamonds among the mounds of coal. Would like to see more recent results of those trials. Much potential research here.

[Scout4answers]

They all seem to work on different pathways , finding the right cocktail is the challenge.

I am intrigued by the results of our brother posters that are able to achieve multiple years of remission using multiple supplements and drugs.

I want to unlock the right combo that will work for the rest of us.