Mitochondrially targeted tamoxifen as anticancer therapy: case series of patients with renal cell carcinoma treated in a phase I/Ib clinical trial

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F23%3A00576613" target="_blank" >RIV/86652036:_____/23:00576613 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/23:10469324 RIV/00216208:11310/23:10469324 RIV/00216208:11120/23:43926061 RIV/00216208:11320/23:10469324 and 3 more

Result on the web

<a href="https://journals.sagepub.com/doi/10.1177/17588359231197957" target="_blank" >https://journals.sagepub.com/doi/10.1177/17588359231197957</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/17588359231197957" target="_blank" >10.1177/17588359231197957</a>

Result language

angličtina

Original language name

Mitochondrially targeted tamoxifen as anticancer therapy: case series of patients with renal cell carcinoma treated in a phase I/Ib clinical trial

Original language description

Mitochondrially targeted anticancer drugs (mitocans) that disrupt the energy-producing systems of cancer are emerging as new potential therapeutics. Mitochondrially targeted tamoxifen (MitoTam), an inhibitor of mitochondrial respiration respiratory complex I, is a first-in-class mitocan that was tested in the phase I/Ib MitoTam-01 trial of patients with metastatic cancer. MitoTam exhibited a manageable safety profile and efficacy, among 37% (14/38) of responders, the efficacy was greatest in patients with metastatic renal cell carcinoma (RCC) with a clinical benefit rate of 83% (5/6) of patients. This can be explained by the preferential accumulation of MitoTam in the kidney tissue in preclinical studies. Here we report the mechanism of action and safety profile of MitoTam in a case series of RCC patients. All six patients were males with a median age of 69 years, who had previously received at least three lines of palliative systemic therapy and suffered progressive disease before starting MitoTam. We recorded stable disease in four, partial response in one, and progressive disease (PD) in one patient. The histological subtype matched clear cell RCC (ccRCC) in the five responders and claro-cellular carcinoma with sarcomatoid features in the non-responder. The number of circulating tumor cells (CTCs) was evaluated longitudinally to monitor disease dynamics. Beside the decreased number of CTCs after MitoTam administration, we observed a significant decrease of the mitochondrial network mass in enriched CTCs. Two patients had long-term clinical responses to MitoTam, of 50 and 36 weeks. Both patients discontinued treatment due to adverse events, not PD. Two patients who completed the trial in November 2019 and May 2020 are still alive without subsequent anticancer therapy. The toxicity of MitoTam increased with the dosage but was manageable. The efficacy of MitoTam in pretreated ccRCC patients is linked to the novel mechanism of action of this first-in-class mitochondrially targeted drug.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

<a href="/en/project/NU21-03-00545" target="_blank" >NU21-03-00545: Mitochondrially targeted tamoxifen in renal cancer treatment</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Therapeutic Advances in Medical Oncology

ISSN

1758-8340

e-ISSN

1758-8359

Volume of the periodical

15

Issue of the periodical within the volume

March 28

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

17588359231197957

UT code for WoS article

001073174100001

EID of the result in the Scopus database

2-s2.0-85173719121