Use of Rx drugs and botanical compoun... - Advanced Prostate...

Advanced Prostate Cancer

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Use of Rx drugs and botanical compounds to prevent chemo drug-resistance with Docetaxel.

chillpill7 profile image
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Docetaxel is a common therapuetic used in advanced prostate cancers. There are some combinations you can ask your doctor about that will definitely and safely maximize its effects.

Obviously we all all heard of radiation resistance but there is also such a thing as chemo drug-resistance. Countless research articles point out the synergisms between botanical compounds that can increase the likelhood of the chemo being completly effective in destroying tumor cells and thus prevent the need for further chemos or radiation etc.

Its like a bacterial infection. We know that certian bacteria's have built a resistance to antibiotics but by combining antibiotics with simple natural ingredient compounds researchers and doctors are now finding new ways to overcome the bacteria's defenses. This is a well known fact and the same goes for cancer, radiation and chemotherapuetics.

If you or a loved one is on a chemotherapuetic like docetaxel there are indeed simple things you can do like taking turmeric, green tea, resveratrol, flavonoids, noscapine etc. that could massivley improve your chances of overcoming this without the cancer developing drug-resistance. Furthermore, these natural botanical ingredients will not only help the effectiveness of the chemo but also protect the body from systemic toxicities. These are known to be completely safe botanicals and natural compounds that are found in small amounts in virtually any vegetable or fruit you can think of.

Most likely your doctor will not know about the natural/ botanical compounds that synergize with the chemo and thus not recommend them. Most doctors are nervous about taking other things with chemo because of the possible negative interactions. However, there are also compounds like the handful listed below that show positive benefits when taken with chemo. There has already been more than enough research demonstrating that these natural botanical products are completely safe.

Like with all things do your own research and come to your own conclusion on whether you would benefit with such protocols. However I would say in most cases I believe that the benefits greatly outweigh the disadvantages.

The following article will outline the issue with chemo resistance.

In addition to the promising therapeutic cancer vaccines and newly developed agents targeting androgen receptor signaling, chemotherapy-based treatments will likely continue to play a significant role in patients with mCRPC. Recently published data that showed that a second taxane (cabazitaxel) extends survival after progression on docetaxel was a significant step forward, but also highlighted the need to overcome taxane resistance in prostate cancer.

clincancerres.aacrjournals....

Prescription drugs that synergize with docetaxel and are known as chemosensitizers.

1. Rapamycin

Combination of Rapamycin and docetaxel reduces prostate and breast cancer cell VEGF production and tumour vascularisation independently of sphingosine-kinase-1

nature.com/articles/s41598-...

Rapamycin- mTOR inhibition overcomes docetaxel chemoresistance in prostate cancer cell and mouse models through downregulation of sphingosine kinase

ejcancer.com/article/S0959-...

Rapamycin enhances docetaxel-induced cytotoxicity in a androgen-independent prostate cancer xenograft model by survivin downregulation

-The rapamycin-dependent enhancement of the cytotoxic effects of docetaxel was associated with the downregulation of survivin expression. Our results suggest that the combination of docetaxel and rapamycin is a candidate for the improved treatment of advanced prostate cancer.

sciencedirect.com/science/a...

2. Metformin

“Metformin may be an effective chemosensitizer for docetaxel,” said Marc P. Martin, of the Centre Antoine Lacassagne in Nice, France. The anti-diabetic medication has low cost and minimal side effects, and it is known to decrease prostate cancer incidence and improve time to castration resistance and survival in prostate cancer patients who are diabetic. Martin presented results of the study (abstract 5004) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago.

ar.iiarjournals.org/content...

3. Enzalutamide (xtandi) ADT (androgen deprivation therapy)

First-line enzalutamide, docetaxel combination improves disease control in advanced prostate cancer

February 15, 2019

healio.com/hematology-oncol...

4. OGX-011

In conclusion, docetaxel/prednisone with OGX-011 was well tolerated as first-line therapy in patients with metastatic CRPC, and there was evidence of a biologic effect with decreases in serum clusterin. Given the robust preclinical data supporting clusterin as a therapeutic target, clinical data demonstrating OGX-011 on-target effects, and the suggestion of improved survival outcomes for patients treated with docetaxel and OGX-011, further evaluation of the combination is warranted.

Natural Botanical Ingredients that synergize with docetaxel (chemosensitizers)

The advantage to botanical compounds is they are much safer and less expensive.

1. Curcumin

Similar studies have also revealed that curcmunin can sensitize a variety of tumors to gamma radiation including glioma, neuroblastoma, cervical carcinoma, epidermal carcinoma, prostate cancer, and colon cancer. How curcumin acts as a chemosensitizer and radiosensitizer has also been studied extensively. For example, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-κB, STAT3, COX2, Akt, antiapoptotic proteins, growth factor receptors, and multidrug-resistance proteins. Although it acts as a chemosensitizer and radiosensitizer for tumors in some cases, curcumin has also been shown to protect normal organs such as liver, kidney, oral mucosa, and heart from chemotherapy and radiotherapy-induced toxicity.

tandfonline.com/doi/abs/10....

2. Quercetin and other plant flavonoids like apigenin, luteolin, chrysin

, hesperetin, baicalein and naringenin

iioab.org/articles/IIOABJ_7...

Chrysin Increases the Therapeutic Efficacy of Docetaxel and Mitigates Docetaxel-Induced Edema

ncbi.nlm.nih.gov/pubmed/271...

ncbi.nlm.nih.gov/pubmed/303...

3. Resveratrol and emodin

Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro

orbit.dtu.dk/ws/files/17117...

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

Resveratrol induces cell cycle arrest and apoptosis with docetaxel in prostate cancer cells via a p53/ p21WAF1/CIP1 and p27KIP1 pathway

In conclusion, our study demonstrates the therapeutic efficacy of resveratrol in combination with low dosages of docetaxel could lead to improving the clinical outcomes of prostate cancer treatment in clinical setting

Emodin:

cancerres.aacrjournals.org/...

4. Noscapine- a natural plant alkaloid that has been proven non-toxic has been used for over a 100 years as a cough suppressant.

Noscapine chemosensitization enhances docetaxel anticancer activity and nanocarrier uptake in triple negative breast cancer

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

In conclusion, to our knowledge this study is the first attempt to identify a combination of Noscapine pre-sensitization at low concentrations in conjunction with Docetaxel inhibits growth of wild type and drug-resistant tumor cells illustrated in vitro as well as in vivo (Fig. 6). Noscapine oral administration enhanced the anticancer activity of docetaxel in drug resistant tumors by enhancing the tumor bioavailability of docetaxel and chemo-sensitizing the tumor to docetaxel. This study provides a basis for improving efficacy of chemotherapy effect on drug resistant tumors and sheds light on new insights to the development of novel clinical therapeutics.

Noscapine Inhibits Human Prostate Cancer Progression and Metastasis in a Mouse Model

Noscapine, a non-toxic alkaloid and common constituent of cough medicine, stabilises tubulin. It inhibits the growth of several human and murine neoplasms, with no significant toxicity. Oral administration of noscapine limited tumour growth and lymphatic metastasis of PC3 human prostate cancer in this mouse model, supporting its therapeutic potential as a nontoxic and easily administered treatment for metastatic cancer.

5. Artemisinin

6.2. Artemisinin and Its Derivatives Used to Sensitize Cancer Cells

Another characteristic of tumors and cancer cells is their ability to develop resistance to chemotherapy due to their rapid cell division rate and genetic mutations [57]. Artemisinin has proved to turn resistant cancer cells into sensitive cancer cells, a term called chemosensitization [6]. Reungpatthanaphong found that artemisinin, artesunate, and dihydroartemisinin, when combined with doxorubicin and pirarubicin, increased their cytotoxicity against P-glycoprotein-overexpressing K562/ADR, and in MRP1-overexpressing GLC4/ADR cell lines [58]. Some artemisinin derivatives have also shown to inhibit the P-glycoprotein in the blood brain barrier, making them a candidate for brain cancer therapies [59]. Wang and colleagues reported that artesunate sensitized ovarian cancer cells to cisplatin through down regulation of RAD51, a protein that repairs DNA double strand breaks, inhibiting the clonogenic formation of those cancer cells [60]. Hou and colleagues reported that regardless of p53 status in hepatoma cells, artemisinin, and its derivatives proved to be a powerful chemosensitization agent [61].

Artemisinin is not exempt from resistance by cancer cells, and while Plasmodium resistance to artemisinin and its derivatives has become increasingly common [62,63], there are few reports on cancer cells becoming resistant to artemisinin or its derivatives, probably because of the many possible modes of action of the drug [6]. Bachmeier reported in a study conducted with metastatic breast cancer cells that resistance was developed by induction of transcription factors NFκB and activator protein 1 (AP-1) [64]. On a similar note, Anfosso and colleagues performed microarray techniques to support the fact that resistance and sensitivity can be predicted through messenger RNA (mRNA) analysis of angiogenesis related genes, such as VEGF [65].

7. EGCG from Green Tea

Sensitization to docetaxel in prostate cancer cells by green tea and quercetin

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

Synergistic Effects of the Green Tea Extract Epigallocatechin-3-gallate and Taxane in Eradication of Malignant Human Prostate Tumors

In mice treated with EGCG plus taxane, the disease-free survival rates increased from 0% (in untreated mice) to more than 70% to 80% in treated mice. Taken together, these data demonstrate for the first time that EGCG in combination with taxane may provide a novel therapeutic treatment of advanced prostate cancer.

8. Genistein

Genistein, derived from soybeans, has been found to inhibit cancer cell growth without toxicity. We have recently reported that genistein could potentiate the antitumor activity of chemotherapeutic agents both in vitro and in vivo. However, the molecular mechanism of this novel effect of genistein has not been fully elucidated. In this study, we found that genistein significantly potentiated the antitumor, anti-invasive, and antimetastatic activities of docetaxel both in culture and in severe combined immunodeficient (SCID)-human model of experimental prostate cancer bone metastasis

From these results, we conclude that genistein could be a promising nontoxic agent to improve the treatment outcome of metastatic prostate cancer with docetaxel.

ncbi.nlm.nih.gov/pubmed/166...

ncbi.nlm.nih.gov/pubmed/185...

Again most doctors will not know about this research of using drug and or botanical ingredients to work in synergism with the chemo. They will likely be hestiant to use something else with it. I understand this reasoning but if taking a couple capsules of something that is already proven safe like turmeric root (curcumin) or noscapine (which has been used in cough medications for over 100 years) can improve the chemo's therapuetic effect it may be worth wild.

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Scott1963

This is really a good post.

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