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Cancer Research News & Studies / Overcoming Problems Of Chemotherapy
« Last post by danialthomas on May 15, 2022, 06:09:57 pm »Cytotoxic chemotherapy remains a primary treatment option to fight cancer. There are three main problems with chemotherapy that must be dealt with if you intend to beat cancer and maintain a decent quality of life:
1. Drug resistance: In metastatic cancer, chemotherapy is rarely curative. Drug resistance limits its therapeutic effectiveness. Resistance can be either pre-existent (intrinsic resistance) or induced by drugs (acquired resistance).
2. Cancer stem cells: These are a small subpopulation of resting cancer cells within a tumor. Cancer stem cells are a leading cause of metastasis and cancer recurrence. Most standard chemotherapy drugs are designed to target rapidly dividing cells. Due to their low proliferation rate, chemotherapy preferentially spares cancer stem cells. Not only does chemotherapy fail to target cancer stem cells, it can do the exact opposite and stimulate them to proliferate and spread.
3. Side effects: Most standard chemotherapies kill cells by a process known as indiscriminate cytotoxicity. Consequently, standard- or full-dose chemotherapy is indiscriminate and has a low safety profile. There will likely be collateral damage. Chemotherapy drugs not only target rapidly dividing cancer cells, but due to their systemic toxicity, normal cells will also be affected. This can cause serious side effects, including damage to the heart, lungs, liver, kidneys, and nervous system.
The solution to circumventing drug resistance is to chemosensitize cancer cells. This makes them more vulnerable to the cytotoxic effects chemotherapy. It may also lessen the dose of chemotherapy needed to induce apoptosis (death) of cancer cells which, in turn, can lessen the side effects. Natural compounds that have been found to be chemosensitizers include berberine, curcumin, EGCG, quercetin, resveratrol, solamargine, sulforaphane, and high-dose intravenous vitamin C. Medications include 2-deoxy-D-glucose, artesunate, fenofibrate, itraconazole, ivermectin, and pentoxifylline.
There are no drugs yet that are FDA-approved to target cancer stem cells. To address this urgent and unmet need, the following natural compounds and prescription medication should be considered, as they have been found to target cancer stem cells by killing them and/or preventing them from entering a dormant and more resistant state: Bergamot, curcumin, EGCG, genistein, resveratrol, sodium selenite, sulforaphane, tadalafil, and intravenous vitamin C with low-dose azithromycin and doxycycline.
To help protect yourself during chemotherapy, if your oncologist will not agree to administering low-dose chemotherapy, chemoprotectants should be considered. These are compounds that can reduce the toxic effects of chemotherapy without compromising the anticancer effects. The natural products and prescription medications that can reduce the damage from chemotherapy include ashwagandha, berberine, bitter melon, curcumin, lycopene, melatonin, resveratrol, and pentoxifylline.
Dr. Daniel Thomas, DO, MS
Mount Dora, Florida
References:
Aghaee F, Pirayesh Islamian J, Baradaran B. Enhanced radiosensitivity and chemosensitivity of breast cancer cells by 2-deoxy-D-glucose in combination therapy. J Breast Cancer. 2012 Jun;15(2):141-7.
Barancik M, Bohacova V, Gibalova L, Sedlak J, Sulova Z, Breier A. Potentiation of anticancer drugs: effects of pentoxifylline on neoplastic cells. Int J Mol Sci. 2012;13(1):369-382.
Cham, B. (2017) Solasodine, Solamargine and Mixtures of Solasodine Rhamnosides: Pathway to Expansive Clinical Anticancer Therapies. International Journal of Clinical Medicine, 8, 692-713.
Cham, B. Combination Treatment with BEC and Cisplatin Synergistically Augments Anticancer Activity and Results in Increased Absolute Survival. Journal of Cancer Therapy, Vol.11 No.8, 2020.
Chen W, An J, Guo J, Wu Y, Yang L, Dai J, Gong K, Miao S, Xi S, Du J. Sodium selenite attenuates lung adenocarcinoma progression by repressing SOX2-mediated stemness. Cancer Chemother Pharmacol. 2018 May;81(5):885-895.
De Francesco EM, Sotgia F, Lisanti MP. Cancer stem cells (CSCs): metabolic strategies for their identification and eradication. Biochem J. 2018;475(9):1611-1634.
Devarajan N, Jayaraman S, Mahendra J, Venkatratnam P, Rajagopal P, Palaniappan H, Ganesan SK. Berberine-A potent chemosensitizer and chemoprotector to conventional cancer therapies. Phytother Res. 2021 Jun;35(6):3059-3077.
Fan LX, Liu CM, Gao AH, Zhou YB, Li J. Berberine combined with 2-deoxy-d-glucose synergistically enhances cancer cell proliferation inhibition via energy depletion and unfolded protein response disruption. Biochim Biophys Acta. 2013 Nov;1830(11):5175-83.
Fiorillo M, Peiris-Pagès M, Sanchez-Alvarez R, Bartella L, Di Donna L, Dolce V, Sindona G, Sotgia F, Cappello AR, Lisanti MP. Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism. Biochim Biophys Acta Bioenerg. 2018 Sep;1859(9):984-996.
Fiorillo M, Tóth F, Sotgia F, Lisanti MP. Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs). Aging (Albany NY). 2019 Apr 19;11(
:2202-2216.
Golunski G, Woziwodzka A, Piosik J. Potential Use of Pentoxifylline in Cancer Therapy. Curr Pharm Biotechnol. 2018;19(3):206-216.
Hamed, A.R., Abdel-Azim, N.S., Shams, K.A. et al. Targeting multidrug resistance in cancer by natural chemosensitizers. Bull Natl Res Cent 43, 8 (2019).
Jiang L, Wang P, Sun YJ, Wu YJ. Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway. J Exp Clin Cancer Res. 2019 Jun 18;38(1):265.
Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res. 2018;8(2):317-331.
Klutzny, S., Anurin, A., Nicke, B. et al. PDE5 inhibition eliminates cancer stem cells via induction of PKA signaling. Cell Death Dis 9, 192 (2018).
Liang CH, Liu LF, Shiu LY, Huang YS, Chang LC, Kuo KW. Action of solamargine on TNFs and cisplatin-resistant human lung cancer cells. Biochem Biophys Res Commun. 2004 Sep 24;322(3):751-8.
Li S, Liao R, Sheng X, et al. Hydrogen Gas in Cancer Treatment. Front Oncol. 2019;9:696. Published 2019 Aug 6.
Liu H, Kurtoglu M, León-Annicchiarico CL, et al. Combining 2-deoxy-D-glucose with fenofibrate leads to tumor cell death mediated by simultaneous induction of energy and ER stress. Oncotarget. 2016;7(24):36461-36473.
Ma Z, Xu L, Liu D, et al. Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing. Oxid Med Cell Longev. 2020;2020:6841581.
Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, Siegelin MD, Fimognari C, Kumar NB, Dou QP, Yang H, Samadi AK, Russo GL, Spagnuolo C, Ray SK, Chakrabarti M, Morre JD, Coley HM, Honoki K, Fujii H, Georgakilas AG, Amedei A, Niccolai E, Amin A, Ashraf SS, Helferich WG, Yang X, Boosani CS, Guha G, Bhakta D, Ciriolo MR, Aquilano K, Chen S, Mohammed SI, Keith WN, Bilsland A, Halicka D, Nowsheen S, Azmi AS. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 2015 Dec;35 Suppl(0):S78-S103.
Monu, Pushpa C. Tomar, Shilpa S. Chapadgaonkar. Natural Chemoprotectants for Mitigating the Side Effects of Cancer Therapy. Ambient Science, 2019: Vol. 06(Sp1); Online.
Naujokat C, McKee DL. The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein. Curr Med Chem. 2020 Feb 27.
Pounds R, Leonard S, Dawson C, Kehoe S. Repurposing itraconazole for the treatment of cancer. Oncol Lett. 2017;14(3):2587-2597.
Raimundo Gonçalves de Oliveira Júnior, Alves Ferraz Christiane Adrielly, Jackson Roberto Guedes da Silva Almeida, Raphaël Grougnet, Valérie Thiéry, Laurent Picot, Sensitization of tumor cells to chemotherapy by natural products: A systematic review of preclinical data and molecular mechanisms, Fitoterapia, Volume 129, 2018, Pages 383-400.
Sun J, Zheng Z, Chen Q, Pan Y, Quan M, Dai Y. Fenofibrate potentiates chemosensitivity to human breast cancer cells by modulating apoptosis via AKT/NF-κB pathway. Onco Targets Ther. 2019 Jan 23;12:773-783.
Wang B, Hou D, Liu Q, Wu T, Guo H, Zhang X, Zou Y, Liu Z, Liu J, Wei J, Gong Y, Shao C. Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51. Cancer Biol Ther. 2015;16(10):1548-56.
Zhang F, Aft RL. Chemosensitizing and cytotoxic effects of 2-deoxy-D-glucose on breast cancer cells. J Cancer Res Ther. 2009 Sep;5 Suppl 1:S41-3.
Zhang QY, Wang FX, Jia KK, Kong LD. Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects. Front Pharmacol. 2018;9:1253.
Disclaimer:
This information is strictly for educational purposes only and not intended or implied to be personal medical advice. That is for your personal physician to provide after he or she accesses and reads each of the references above.
1. Drug resistance: In metastatic cancer, chemotherapy is rarely curative. Drug resistance limits its therapeutic effectiveness. Resistance can be either pre-existent (intrinsic resistance) or induced by drugs (acquired resistance).
2. Cancer stem cells: These are a small subpopulation of resting cancer cells within a tumor. Cancer stem cells are a leading cause of metastasis and cancer recurrence. Most standard chemotherapy drugs are designed to target rapidly dividing cells. Due to their low proliferation rate, chemotherapy preferentially spares cancer stem cells. Not only does chemotherapy fail to target cancer stem cells, it can do the exact opposite and stimulate them to proliferate and spread.
3. Side effects: Most standard chemotherapies kill cells by a process known as indiscriminate cytotoxicity. Consequently, standard- or full-dose chemotherapy is indiscriminate and has a low safety profile. There will likely be collateral damage. Chemotherapy drugs not only target rapidly dividing cancer cells, but due to their systemic toxicity, normal cells will also be affected. This can cause serious side effects, including damage to the heart, lungs, liver, kidneys, and nervous system.
The solution to circumventing drug resistance is to chemosensitize cancer cells. This makes them more vulnerable to the cytotoxic effects chemotherapy. It may also lessen the dose of chemotherapy needed to induce apoptosis (death) of cancer cells which, in turn, can lessen the side effects. Natural compounds that have been found to be chemosensitizers include berberine, curcumin, EGCG, quercetin, resveratrol, solamargine, sulforaphane, and high-dose intravenous vitamin C. Medications include 2-deoxy-D-glucose, artesunate, fenofibrate, itraconazole, ivermectin, and pentoxifylline.
There are no drugs yet that are FDA-approved to target cancer stem cells. To address this urgent and unmet need, the following natural compounds and prescription medication should be considered, as they have been found to target cancer stem cells by killing them and/or preventing them from entering a dormant and more resistant state: Bergamot, curcumin, EGCG, genistein, resveratrol, sodium selenite, sulforaphane, tadalafil, and intravenous vitamin C with low-dose azithromycin and doxycycline.
To help protect yourself during chemotherapy, if your oncologist will not agree to administering low-dose chemotherapy, chemoprotectants should be considered. These are compounds that can reduce the toxic effects of chemotherapy without compromising the anticancer effects. The natural products and prescription medications that can reduce the damage from chemotherapy include ashwagandha, berberine, bitter melon, curcumin, lycopene, melatonin, resveratrol, and pentoxifylline.
Dr. Daniel Thomas, DO, MS
Mount Dora, Florida
References:
Aghaee F, Pirayesh Islamian J, Baradaran B. Enhanced radiosensitivity and chemosensitivity of breast cancer cells by 2-deoxy-D-glucose in combination therapy. J Breast Cancer. 2012 Jun;15(2):141-7.
Barancik M, Bohacova V, Gibalova L, Sedlak J, Sulova Z, Breier A. Potentiation of anticancer drugs: effects of pentoxifylline on neoplastic cells. Int J Mol Sci. 2012;13(1):369-382.
Cham, B. (2017) Solasodine, Solamargine and Mixtures of Solasodine Rhamnosides: Pathway to Expansive Clinical Anticancer Therapies. International Journal of Clinical Medicine, 8, 692-713.
Cham, B. Combination Treatment with BEC and Cisplatin Synergistically Augments Anticancer Activity and Results in Increased Absolute Survival. Journal of Cancer Therapy, Vol.11 No.8, 2020.
Chen W, An J, Guo J, Wu Y, Yang L, Dai J, Gong K, Miao S, Xi S, Du J. Sodium selenite attenuates lung adenocarcinoma progression by repressing SOX2-mediated stemness. Cancer Chemother Pharmacol. 2018 May;81(5):885-895.
De Francesco EM, Sotgia F, Lisanti MP. Cancer stem cells (CSCs): metabolic strategies for their identification and eradication. Biochem J. 2018;475(9):1611-1634.
Devarajan N, Jayaraman S, Mahendra J, Venkatratnam P, Rajagopal P, Palaniappan H, Ganesan SK. Berberine-A potent chemosensitizer and chemoprotector to conventional cancer therapies. Phytother Res. 2021 Jun;35(6):3059-3077.
Fan LX, Liu CM, Gao AH, Zhou YB, Li J. Berberine combined with 2-deoxy-d-glucose synergistically enhances cancer cell proliferation inhibition via energy depletion and unfolded protein response disruption. Biochim Biophys Acta. 2013 Nov;1830(11):5175-83.
Fiorillo M, Peiris-Pagès M, Sanchez-Alvarez R, Bartella L, Di Donna L, Dolce V, Sindona G, Sotgia F, Cappello AR, Lisanti MP. Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism. Biochim Biophys Acta Bioenerg. 2018 Sep;1859(9):984-996.
Fiorillo M, Tóth F, Sotgia F, Lisanti MP. Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs). Aging (Albany NY). 2019 Apr 19;11(

Golunski G, Woziwodzka A, Piosik J. Potential Use of Pentoxifylline in Cancer Therapy. Curr Pharm Biotechnol. 2018;19(3):206-216.
Hamed, A.R., Abdel-Azim, N.S., Shams, K.A. et al. Targeting multidrug resistance in cancer by natural chemosensitizers. Bull Natl Res Cent 43, 8 (2019).
Jiang L, Wang P, Sun YJ, Wu YJ. Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-κB pathway. J Exp Clin Cancer Res. 2019 Jun 18;38(1):265.
Juarez M, Schcolnik-Cabrera A, Dueñas-Gonzalez A. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. Am J Cancer Res. 2018;8(2):317-331.
Klutzny, S., Anurin, A., Nicke, B. et al. PDE5 inhibition eliminates cancer stem cells via induction of PKA signaling. Cell Death Dis 9, 192 (2018).
Liang CH, Liu LF, Shiu LY, Huang YS, Chang LC, Kuo KW. Action of solamargine on TNFs and cisplatin-resistant human lung cancer cells. Biochem Biophys Res Commun. 2004 Sep 24;322(3):751-8.
Li S, Liao R, Sheng X, et al. Hydrogen Gas in Cancer Treatment. Front Oncol. 2019;9:696. Published 2019 Aug 6.
Liu H, Kurtoglu M, León-Annicchiarico CL, et al. Combining 2-deoxy-D-glucose with fenofibrate leads to tumor cell death mediated by simultaneous induction of energy and ER stress. Oncotarget. 2016;7(24):36461-36473.
Ma Z, Xu L, Liu D, et al. Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing. Oxid Med Cell Longev. 2020;2020:6841581.
Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, Siegelin MD, Fimognari C, Kumar NB, Dou QP, Yang H, Samadi AK, Russo GL, Spagnuolo C, Ray SK, Chakrabarti M, Morre JD, Coley HM, Honoki K, Fujii H, Georgakilas AG, Amedei A, Niccolai E, Amin A, Ashraf SS, Helferich WG, Yang X, Boosani CS, Guha G, Bhakta D, Ciriolo MR, Aquilano K, Chen S, Mohammed SI, Keith WN, Bilsland A, Halicka D, Nowsheen S, Azmi AS. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 2015 Dec;35 Suppl(0):S78-S103.
Monu, Pushpa C. Tomar, Shilpa S. Chapadgaonkar. Natural Chemoprotectants for Mitigating the Side Effects of Cancer Therapy. Ambient Science, 2019: Vol. 06(Sp1); Online.
Naujokat C, McKee DL. The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein. Curr Med Chem. 2020 Feb 27.
Pounds R, Leonard S, Dawson C, Kehoe S. Repurposing itraconazole for the treatment of cancer. Oncol Lett. 2017;14(3):2587-2597.
Raimundo Gonçalves de Oliveira Júnior, Alves Ferraz Christiane Adrielly, Jackson Roberto Guedes da Silva Almeida, Raphaël Grougnet, Valérie Thiéry, Laurent Picot, Sensitization of tumor cells to chemotherapy by natural products: A systematic review of preclinical data and molecular mechanisms, Fitoterapia, Volume 129, 2018, Pages 383-400.
Sun J, Zheng Z, Chen Q, Pan Y, Quan M, Dai Y. Fenofibrate potentiates chemosensitivity to human breast cancer cells by modulating apoptosis via AKT/NF-κB pathway. Onco Targets Ther. 2019 Jan 23;12:773-783.
Wang B, Hou D, Liu Q, Wu T, Guo H, Zhang X, Zou Y, Liu Z, Liu J, Wei J, Gong Y, Shao C. Artesunate sensitizes ovarian cancer cells to cisplatin by downregulating RAD51. Cancer Biol Ther. 2015;16(10):1548-56.
Zhang F, Aft RL. Chemosensitizing and cytotoxic effects of 2-deoxy-D-glucose on breast cancer cells. J Cancer Res Ther. 2009 Sep;5 Suppl 1:S41-3.
Zhang QY, Wang FX, Jia KK, Kong LD. Natural Product Interventions for Chemotherapy and Radiotherapy-Induced Side Effects. Front Pharmacol. 2018;9:1253.
Disclaimer:
This information is strictly for educational purposes only and not intended or implied to be personal medical advice. That is for your personal physician to provide after he or she accesses and reads each of the references above.