Blocking estrogen stops/slows estrogen-sensitive lung cancer

If a patient's lung cancer displays estrogen receptors, then reducing estrogen levels in the body, in addition to standard treatments, is potentially beneficial (since estrogen stimulates cancer growth).   According to American Association for Cancer Research study published in 2002, human non small cell lung cancer show estrogen receptors and respond to estrogen.  Estrogen dominance is a prevailing problem in today's world.

Laura P. Stabile, Autumn L. Gaither Davis, Christopher T. Gubish, Toni M. Hopkins, James D. Luketich, Neil Christie, Sydney Finkelstein and Jill M. Siegfried. Human Non-Small Cell Lung Tumors and Cells Derived from Normal Lung Express Both Estrogen Receptor α and β and Show Biological Responses to Estrogen.  Cancer Res April 1 2002 (62) (7) 2141-2150; Link

"Our studies continue to show that lung cancer cells grow in response to estrogen and that stopping or slowing the spread of the disease may be dependent on blocking the action of estrogen, in fact, in previous studies, we have observed that lung tumor cells contain estrogen receptors at levels comparable to breast cancer cells."

-   Jill Siegfried, Ph.D., professor, department of pharmacology and co-leader,

Lung and Thoracic Malignancies Program, University of Pittsburgh Cancer Institute.

(A receptor is a structure on the surface of a cell that selectively receives and binds substances)

How to Reduce Estrogen Levels/Activity in the Body

DIM Supplementation in lung cancer

DIM Supplementation (proven to be beneficial in reducing estrogenic activity in the body) demonstrated anti-cancer mechanisms in lung cancer in mice and human studies

Morse MA, LaGreca SD, Amin SG, Chung FL. Effects of indole-3-carbinol on lung tumorigenesis and DNA methylation induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and on the metabolism and disposition of NNK in A/J mice. Cancer Res. 1990;50:2613-7. [PubMed]

Ichite N, Chougule MB, Jackson T, Fulzele SV, Safe S, et al. Enhancement of docetaxel anticancer activity by a novel diindolylmethane compound in human non-small cell lung cancer. Clin Cancer Res. 2009;15:543-552. [PubMed]

I3C / DIM - Estrogen Blocker with Anti-cancer benefits

MELATONIN has multiple anti-estrogen actions and decreases ESTRADIOL levels in the body in lung cancer

MELATONIN has been used both alone and in combination with most standard cancer treatments because it improves both survival and quality of life

Lynch E. Melatonin and cancer treatment. European Biology and Bioelectromagnetics. 2005 Jun 18;1(2):183-200.

Advanced lung cancer patients show a progressive reduction in MELATONIN levels with disrupted sleep-wake patterns

Mazzoccoli G, Giuliani A et al. Decreased serum levels of insulin-like growth factor (IGF)-I in patients with lung cancer: Temporal relationship with growth hormone (GH) levels. Anticancer Res. 1999 Mar;19(2B):1397-9.

Levin RD, Daehler MA et al. Circadian function in patients with advanced non-small-cell lung cancer. Br J Cancer. 2005 Nov 28;93(11):1202-8.

MELATONIN combined with aloe vera extract stabilizes the cancer growth and improves survival in advanced cancer patients.     In a study including 50 patients (with advanced, untreatable neoplasms for whom no other standard treatment is offered) suffering from lung cancer, gastrointestinal tract tumors, breast cancer or brain glioblastoma. Patients were treated with melatonin (MLT) alone (20 mg/day orally when dark) or MLT plus aloe vera tincture (1 ml twice/day).

•  A partial response (PR).    Achieved in 2/24 patients treated with MLT plus aloe and in none of the patients treated with MLT alone.

•  Stable disease (SD).    Achieved in 12/24 and in 7/26 patients treated with MLT plus aloe or MLT alone, respectively.

•  The 1-year survival rate.    Significantly higher in patients treated with MLT plus aloe (9/24 vs. 4/26, p < 0.05).

Lissoni P, Giani L et al. Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms. Nat Immun. 1998;16(1):27-33.

MELATONIN has multiple antiestrogen actions and decreases body's ESTRADIOL levels

Sanchez-Barcelo EJ, Cos S et al. Melatonin-estrogen interactions in breast cancer. J Pineal Res. 2005 May;38(4):217-22.

Rato AG, Pedrero JG et al. Melatonin blocks the activation of estrogen receptor for DNA binding. FASEB J. 1999 May;13(8):857-68.

Study adding MELATONIN to chemotherapy increased survival rates.    100 lung cancer patients were randomized to receive either chemotherapy alone or chemotherapy with melatonin (20 mg/day orally). No patient treated with chemotherapy alone was alive after two years, whereas five-year survival was achieved in three of 49 patients (6 percent) treated with chemotherapy and melatonin. (Lissoni P et al 1999, 2003a,b).

-   Also, lung cancer patients treated with MELATONIN tolerated chemotherapy better and had less-serious side effects

Lissoni P, Barni S et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer. 1999 Nov;35(12):1688-92.

Lissoni P, Chilelli M et al. Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: A randomized trial. J Pineal Res. 2003a Aug;35(1):12-5.

Lissoni P, Malugani F et al. Reduction of cisplatin-induced anemia by the pineal indole 5-methoxytryptamine in metastatic lung cancer patients. Neuro Endocrinol Lett. 2003b Feb;24(1-2):83-5.

Swiss study demonstrated stabilization and increased survival rates in NSCLC patients taking MELATONIN.     A randomized study was designed to evaluate the influence of an MLT treatment (10 mg/day orally at 7.00 p.m.) on the survival time at 1 year from the progression under chemotherapy in respect to supportive care alone in a group of metastatic NSC lung cancer patients, who did not respond to a first-line chemotherapy containing cisplatin. The study includes 63 consecutive metastatic NSCLC patients, who were randomized to receive MLT (n = 31) or supportive care alone (n = 32).

•  The percentage of both stabilizations of disease and survival at 1 year was significantly higher in patients treated with MLT than in those treated only with supportive care

•  No drug-related toxicity was seen in patients treated with MLT.   Who, on the contrary, showed a significant improvement in performance status.

•  This randomized study shows that the pineal hormone MLT may be successfully administered to prolong the survival time in metastatic NSCLC patients who progressed under a first-line chemotherapy with cisplatin.    For whom no other effective therapy is available up to now

Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first- line chemotherapy containing cisplatin. Oncology 1992;49(5):336-339. View Abstract

Vitamin K2 reduces estrogenic activity in body

Vitamin K2 (menaquinone) decreases the ratio of ESTRADIOL to less estrogenic ESTRONE.   Known for its blood coagulation effects, K2 also reduces estrogenic activity.

Otsuka M, Kato N et al. Vitamin K2 binds 17beta-hydroxysteroid dehydrogenase 4 and modulates estrogen metabolism. Life Sci. 2005 Apr 8;76(21):2473-82.

Vitamin K2 - For Klotting and Kalcium

Estrogen levels lowered by maintaining healthy body weight

Body fat is a source of estrogen.    Therefore it is important to establish and maintain a healthy body weight.

Siiteri PK. Adipose tissue as a source of hormones. Am J Clin Nutr. 1987 Jan;45(1 Suppl):277-82.

Possible role for growth factor antagonists in lung cancer?

Peptide hormones act as growth factors and increase lung cancer growth.    E.g. SCLC and NSCLC both produce the growth factors gastrin-releasing peptide (GRP), neurotensin and adrenomedullin, which increase lung cancer growth.

Moody TW. Peptide hormones and lung cancer. Panminerva Med. 2006 Mar;48(1):19-26.

Growth factor antagonists prevent SCLC growth in vitro.    These have been studied in Phase III clinical trials and may provide future treatments for SCLC patients.

Moody TW, Chiles J et al. SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells. Peptides. 2001 Jan;22(1):109-15.

PROGESTERONE Therapy (to deal with estrogen dominance) in lung cancer

Progesterone therapy has had some positive results reversing NSCLC (and estrogen-positive breast cancer) in mice

• Progesterone inhibited growth of Progesterone-positive NSCLC cell lines in mice and in vitro.   A 2005 study by American Association for Cancer Research examined immunolocalization of Progesterone receptor and estrogen receptors in 228 NSCLC cases, and showed that the Progesterone receptor was a potent prognostic factor. Researchers found that Progesterone (at 10 nmol/L in vitro) inhibited the growth of Progesterone receptor-positive NSCLC cell lines, and proposed that the Progesterone receptor is a possible target for Progesterone therapy in NSCLC patients.
• In vivo study (nude mice).    Progesterone significantly reduced the growth of Progesterone receptor-positive NSCLC cells (at ~350 nmol/L serum Progesterone concentration)

Hironori Ishibashi, Takashi Suzuki, Satoshi Suzuki, et al. Progesterone Receptor in Non-Small Cell Lung Cancer--A Potent Prognostic Factor and Possible Target for Endocrine Therapy. Cancer Res 2005;65:6450-6458. Published online July 15, 2005.