- |||||||||| tamoxifen / Generic mfg.
Journal: KRAS-mutated, ER-positive low-grade serous ovarian cancer: Unraveling an exceptional response mystery. (Pubmed Central) - Jun 22, 2021
In vitro investigation revealed that tamoxifen can have agonistic in addition to antagonistic effects, which could be the reason patient was not responding to combination of trametinib and tamoxifen. Our current observations suggest that drugs with different mechanisms of action targeting the same receptor may have markedly different anti-cancer activity when used in combinations.
- |||||||||| metformin / Generic mfg., letrozole / Generic mfg.
Preclinical, Journal: Protective effects of berberine in a rat model of polycystic ovary syndrome mediated via the PI3K/AKT pathway. (Pubmed Central) - Jun 22, 2021
Our current observations suggest that drugs with different mechanisms of action targeting the same receptor may have markedly different anti-cancer activity when used in combinations. The beneficial effects of Ber on PCOS included alterations of the serum hormone levels, recovery of morphological lesions in the ovary, improvement of insulin resistance, and cell viability and inhibition of apoptosis, which were all mediated through the PI3K/AKT pathway.
- |||||||||| tamoxifen / Generic mfg., docetaxel / Generic mfg.
Biomarker, Clinical, P2 data, Journal: Chemotherapy de-escalation using an F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): a multicentre, randomised, open-label, non-comparative, phase 2 trial. (Pubmed Central) - Jun 22, 2021
P2
Hormone receptor-positive patients allocated to group B were additionally given letrozole if postmenopausal (2·5 mg/day orally) or tamoxifen if premenopausal (20 mg/day orally)...Depending on the forthcoming results for the 3-year invasive disease-free survival endpoint, this strategy might be a valid approach to select patients not requiring chemotherapy. F Hoffmann-La Roche.
- |||||||||| letrozole / Generic mfg.
Preclinical, Journal: High Doses of D-Chiro-Inositol Alone Induce a PCO-Like Syndrome and Other Alterations in Mouse Ovaries. (Pubmed Central) - Jun 22, 2021
In contrast, 10-20 mg/day DCIns (human correspondence: 2400-4800 mg/day) produced ovarian lesions resembling those typical of aged mice, and reduced serum testosterone levels without affecting aromatase amounts, suggesting a failure in steroidogenic gonadal activity. Notwithstanding physiological/biochemical differences between mice and humans, the observed pictures of toxicity for ovarian histology and function recommend caution when administering DCIns to PCOS patients at high doses and/or for periods spanning several ovulatory cycles.
- |||||||||| letrozole / Generic mfg.
[VIRTUAL] The mysterious ways of cancer () - Jun 19, 2021 - Abstract #BGCS2021BGCS_223;
Conclusions Both cases are unusual in their clinical presentation and histological findings. They demonstrate the importance of close multi-disciplinary working for an accurate diagnosis in complex cases so that the most appropriate treatment can be offered to patients.
- |||||||||| goserelin acetate / Generic mfg., letrozole / Generic mfg.
[VIRTUAL] Intracardiac extension of low-grade endometrial stromal sarcoma: A case report and review of the literature () - Jun 19, 2021 - Abstract #BGCS2021BGCS_193;
MRI 18-months previous showed a multiple fibroids which were being treated locally with zoladex...Histology confirmed low grade endometrial stromal sarcoma (ESS) and letrozole was initiated...Relapse occurs in 30-50% of patients with 3 years being the median disease free interval. Conclusion This case highlights the presentation of rare disease, accurate histological diagnosis and importance of multidisciplinary team working.
- |||||||||| Ibrance (palbociclib) / Pfizer
Enrollment closed: PATINA: Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer (clinicaltrials.gov) - Jun 15, 2021
P3, N=496, Active, not recruiting,
Conclusion This case highlights the presentation of rare disease, accurate histological diagnosis and importance of multidisciplinary team working. Recruiting --> Active, not recruiting
- |||||||||| letrozole / Generic mfg.
Enrollment change, Trial completion date: LIBER: Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation (clinicaltrials.gov) - Jun 9, 2021
P3, N=170, Active, not recruiting,
Abemaciclib in combination with ET in the East Asian populations of MONARCH 2 and MONARCH 3 provided consistent results with the ITT populations, demonstrating improvements in efficacy with generally tolerable safety profiles for patients with HR+, HER2- advanced breast cancer. N=386 --> 170 | Trial completion date: Feb 2022 --> Aug 2023
- |||||||||| letrozole / Generic mfg.
Clinical, Journal: Long-term response on letrozole for gastric cancer: A case report. (Pubmed Central) - Jun 8, 2021
A patient with ER positive GC with peritoneal dissemination and right axillary lymph node metastasis presented remarkable response to letrozole. The long-term survival obtained using letrozole for a patient with GC with distant metastasis suggests the potential of estrogen targeting hormone therapies for GC.
- |||||||||| letrozole / Generic mfg., anastrozole / Generic mfg., exemestane / Generic mfg.
Journal: Aromatase Inhibitors for the Treatment of Breast Cancer: A Journey from the Scratch. (Pubmed Central) - Jun 4, 2021
The long-term survival obtained using letrozole for a patient with GC with distant metastasis suggests the potential of estrogen targeting hormone therapies for GC. AIs are the mainstream solution of ER+ breast cancer treatment regimen with the continuous improvement of human understanding of the importance of healthy life of women suffering from breast cancer.
- |||||||||| AiRuiKang (dalpiciclib) / Jiangsu Hengrui Pharma
Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy, Metastases: DAWNA-2: A Study of SHR6390 in Combination With Letrozole or Anastrozole in Patients With HR Positive and HER2 Negative Advanced Breast Cancer (clinicaltrials.gov) - Jun 2, 2021
P3, N=426, Active, not recruiting,
AIs are the mainstream solution of ER+ breast cancer treatment regimen with the continuous improvement of human understanding of the importance of healthy life of women suffering from breast cancer. Recruiting --> Active, not recruiting | Trial completion date: Jun 2022 --> Dec 2023 | Trial primary completion date: Dec 2020 --> Dec 2022
- |||||||||| AiRuiKang (dalpiciclib) / Jiangsu Hengrui Pharma
Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy, Metastases: A Study of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Advanced Breast Cancer (clinicaltrials.gov) - Jun 2, 2021
P1/2, N=146, Active, not recruiting,
Recruiting --> Active, not recruiting | Trial completion date: Jun 2022 --> Dec 2023 | Trial primary completion date: Dec 2020 --> Dec 2022 Recruiting --> Active, not recruiting | Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Jun 2019 --> Dec 2021
- |||||||||| cyproterone acetate / Generic mfg.
Retrospective data, Review, Journal: The Effects of Salvia miltiorrhiza on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. (Pubmed Central) - Jun 1, 2021
The studies suggested that S. miltiorrhiza extract combined with letrozole (LET) was more effective in improving pregnancy rate (RR: 2.60, 95% CI: 1.06 to 6.39, P=0.04) compared to LET alone...There was a significant difference between S. miltiorrhiza extract combined with cyproterone acetate (CPA) and CPA alone in terms of decreasing TC (MD: -0.77, 95% CI: -0.89 to -0.65, P < 0.00001), TG (MD: -0.43, 95% CI: -0.65 to -0.20, P < 0.0001), and low-density lipoprotein cholesterol (MD: -0.49, 95% CI: -0.66 to -0.33, P < 0.00001) and increasing high-density lipoprotein cholesterol (MD: 0.30, 95% CI: 0.20, 0.40, P < 0.00001)...The current studies indicate that S. miltiorrhiza has beneficial effects on reproduction and glucose and lipid metabolism in patients with PCOS, and it is generally safe for clinical application. However, more prospective RCTs with large samples, multiple centers, and longer intervention duration are needed in the future to obtain more reliable conclusions.
- |||||||||| Ibrance (palbociclib) / Pfizer
[VIRTUAL] A New ER+Her2- Palbociclib Resistant Breast Cancer PDX Model () - May 30, 2021 - Abstract #EACR2021EACR_3334;
Material and Methods In this PDX study, athymic nude mice bearing either WHIM81 or WHIM84 tumors were treated with 3 different concentrations of Palbociclib (10 mg/kg, 25 mg/kg and 75 mg/kg) administered daily for the duration of the experiment and also included an arm with Fulvestrant administered once weekly through a subcutaneous injection of 3 mg/dose...Conclusion Loss of pRb is an unlikely driver of resistance as WHIM81 retains functional pRb expression based on the presence of phospo-pRb in the tumor. Thus, we believe that WHIM81 will provide a valuable new model to test novel therapies aimed to treat patients with CDK4/6i resistant cancers.
- |||||||||| Ibrance (palbociclib) / Pfizer
[VIRTUAL] A New ER+Her2- Palbociclib Resistant Breast Cancer PDX Model () - May 30, 2021 - Abstract #EACR2021EACR_3333;
Material and Methods In this PDX study, athymic nude mice bearing either WHIM81 or WHIM84 tumors were treated with 3 different concentrations of Palbociclib (10 mg/kg, 25 mg/kg and 75 mg/kg) administered daily for the duration of the experiment and also included an arm with Fulvestrant administered once weekly through a subcutaneous injection of 3 mg/dose...Conclusion Loss of pRb is an unlikely driver of resistance as WHIM81 retains functional pRb expression based on the presence of phospo-pRb in the tumor. Thus, we believe that WHIM81 will provide a valuable new model to test novel therapies aimed to treat patients with CDK4/6i resistant cancers.
- |||||||||| Ibrance (palbociclib) / Pfizer
[VIRTUAL] A New ER+Her2- Palbociclib Resistant Breast Cancer PDX Model () - May 30, 2021 - Abstract #EACR2021EACR_3332;
Material and Methods In this PDX study, athymic nude mice bearing either WHIM81 or WHIM84 tumors were treated with 3 different concentrations of Palbociclib (10 mg/kg, 25 mg/kg and 75 mg/kg) administered daily for the duration of the experiment and also included an arm with Fulvestrant administered once weekly through a subcutaneous injection of 3 mg/dose...Conclusion Loss of pRb is an unlikely driver of resistance as WHIM81 retains functional pRb expression based on the presence of phospo-pRb in the tumor. Thus, we believe that WHIM81 will provide a valuable new model to test novel therapies aimed to treat patients with CDK4/6i resistant cancers.
- |||||||||| Ibrance (palbociclib) / Pfizer
[VIRTUAL] A New ER+Her2- Palbociclib Resistant Breast Cancer PDX Model () - May 30, 2021 - Abstract #EACR2021EACR_3331;
Material and Methods In this PDX study, athymic nude mice bearing either WHIM81 or WHIM84 tumors were treated with 3 different concentrations of Palbociclib (10 mg/kg, 25 mg/kg and 75 mg/kg) administered daily for the duration of the experiment and also included an arm with Fulvestrant administered once weekly through a subcutaneous injection of 3 mg/dose...Conclusion Loss of pRb is an unlikely driver of resistance as WHIM81 retains functional pRb expression based on the presence of phospo-pRb in the tumor. Thus, we believe that WHIM81 will provide a valuable new model to test novel therapies aimed to treat patients with CDK4/6i resistant cancers.
- |||||||||| pictilisib (GDC-0941) / Roche, buparlisib (BKM120) / Novartis, Adlai Nortye
[VIRTUAL] Impact of PI3K inhibition in AIs-treated sensitive and resistant breast cancer cells: anti-proliferative effects and induction of apoptosis () - May 30, 2021 - Abstract #EACR2021EACR_1691;
The third-generation of aromatase inhibitors (AIs), anastrozole (Ana), letrozole (Let) and exemestane (Exe) are a first-line treatment option for estrogen receptor-positive (ER+ ) breast tumors, in postmenopausal women...Therefore, in this work the combinations of two PI3K class I inhibitors, buparlisib (BKM120) and pictilisib (GDC-0941), with AIs were explored in AIs-sensitive (MCF-7aro) and AIs-resistant (LTEDaro) breast cancer cell models...All the combinations in the resistant cells induced apoptosis, through mitochondrial pathway, with a more pronounced effect for the combinations with Exe. Conclusion Despite the high toxicity associated with the use of PI3K class I inhibitors, these results support further studies combining new, less toxic and specific PI3K class I inhibitors with AIs, especially with Exe, in refractory ER+ tumors The authors thank Fundação para a Ciência e Tecnologia (FCT) for T. Augusto PhD grant (BD/128333/2017) funded in part by FCT PhD Programme in Medicines and Pharmaceutical Innovation (i3DU), for C. Amaral contract (DL 57/2016 – Norma Transitória) and by Post-doc grant (SFRH/BPD/98304/2013) and for financial support (UIDP/04378/2020, UIDB/04378/2020).
- |||||||||| pictilisib (GDC-0941) / Roche, buparlisib (BKM120) / Novartis, Adlai Nortye
[VIRTUAL] Impact of PI3K inhibition in AIs-treated sensitive and resistant breast cancer cells: anti-proliferative effects and induction of apoptosis () - May 30, 2021 - Abstract #EACR2021EACR_1690;
The third-generation of aromatase inhibitors (AIs), anastrozole (Ana), letrozole (Let) and exemestane (Exe) are a first-line treatment option for estrogen receptor-positive (ER+ ) breast tumors, in postmenopausal women...Therefore, in this work the combinations of two PI3K class I inhibitors, buparlisib (BKM120) and pictilisib (GDC-0941), with AIs were explored in AIs-sensitive (MCF-7aro) and AIs-resistant (LTEDaro) breast cancer cell models...All the combinations in the resistant cells induced apoptosis, through mitochondrial pathway, with a more pronounced effect for the combinations with Exe. Conclusion Despite the high toxicity associated with the use of PI3K class I inhibitors, these results support further studies combining new, less toxic and specific PI3K class I inhibitors with AIs, especially with Exe, in refractory ER+ tumors The authors thank Fundação para a Ciência e Tecnologia (FCT) for T. Augusto PhD grant (BD/128333/2017) funded in part by FCT PhD Programme in Medicines and Pharmaceutical Innovation (i3DU), for C. Amaral contract (DL 57/2016 – Norma Transitória) and by Post-doc grant (SFRH/BPD/98304/2013) and for financial support (UIDP/04378/2020, UIDB/04378/2020).
- |||||||||| pictilisib (GDC-0941) / Roche, buparlisib (BKM120) / Novartis, Adlai Nortye
[VIRTUAL] Impact of PI3K inhibition in AIs-treated sensitive and resistant breast cancer cells: anti-proliferative effects and induction of apoptosis () - May 30, 2021 - Abstract #EACR2021EACR_1689;
The third-generation of aromatase inhibitors (AIs), anastrozole (Ana), letrozole (Let) and exemestane (Exe) are a first-line treatment option for estrogen receptor-positive (ER+ ) breast tumors, in postmenopausal women...Therefore, in this work the combinations of two PI3K class I inhibitors, buparlisib (BKM120) and pictilisib (GDC-0941), with AIs were explored in AIs-sensitive (MCF-7aro) and AIs-resistant (LTEDaro) breast cancer cell models...All the combinations in the resistant cells induced apoptosis, through mitochondrial pathway, with a more pronounced effect for the combinations with Exe. Conclusion Despite the high toxicity associated with the use of PI3K class I inhibitors, these results support further studies combining new, less toxic and specific PI3K class I inhibitors with AIs, especially with Exe, in refractory ER+ tumors The authors thank Fundação para a Ciência e Tecnologia (FCT) for T. Augusto PhD grant (BD/128333/2017) funded in part by FCT PhD Programme in Medicines and Pharmaceutical Innovation (i3DU), for C. Amaral contract (DL 57/2016 – Norma Transitória) and by Post-doc grant (SFRH/BPD/98304/2013) and for financial support (UIDP/04378/2020, UIDB/04378/2020).
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