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Methods of treating cancer and preventing drug resistance

A cancer and resistance technology, applied in drug combinations, pharmaceutical formulations, anti-tumor drugs, etc., can solve problems such as unclear role of tumor cell subgroups, and achieve the effect of reducing side effects

Inactive Publication Date: 2015-10-21
F HOFFMANN LA ROCHE & CO AG
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Problems solved by technology

Although some specific resistance-conferring mutations have been identified in many cancer patients exhibiting acquired drug resistance, the relative contributions of mutated and non-mutated mechanisms to drug resistance and the role of each tumor cell subset remain somewhat unclear

Method used

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  • Methods of treating cancer and preventing drug resistance
  • Methods of treating cancer and preventing drug resistance
  • Methods of treating cancer and preventing drug resistance

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Embodiment 1

[0236] Materials and methods

[0237] Human Cancer Cell Lines and Reagents

[0238] in RPMI medium supplemented with sodium pyruvate, 10% fetal bovine serum, and the antibiotics penicillin and streptomycin at 37°C in 5% CO 2 Human cancer cell lines were cultured in the presence.

[0239] ALDH activity assay

[0240] ALDH activity was detected using a bodipy-labeled ALDH substrate (Aldefluor Kit, Stem Cell Technology) reconstituted according to the supplier's protocol. Substrate was diluted in RPMI medium (5ul substrate / ml medium) and added to adherent cells. at 37°C in CO 2 After 30 minutes of incubation in the incubator, cells were washed twice with RPMI medium, and images were collected using an IncuCyte HD System (Essen BioScience) with a 10× objective.

[0241] Flow cytometry and RNA extraction

[0242] ALDH activity in Kato II parental cells was detected using the Aldefluor assay. ALDH representing ~5% of parental cells with highest and lowest ALDH activity, respec...

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Abstract

Provided herein are pharmaceutical products comprising therapeutically effective combinations of ALDH inhibitors (e.g., disulfiram and / or derivatives thereof) and targeted therapeutics, as well as methods of using said combinations for the treatment of cancer.

Description

field of invention [0001] Provided herein are therapies for the treatment of pathological conditions, such as cancer, using ALDH inhibitors and targeted therapeutics. Background of the invention [0002] The relatively rapid acquisition of resistance to cancer drugs remains a key obstacle to successful cancer therapy. Significant efforts to elucidate the molecular basis of such drug resistance have revealed multiple mechanisms, including drug efflux, acquisition of drug-binding-deficient mutants of the target, involvement of alternative survival pathways, epigenetic alterations. Such mechanisms are generally thought to reflect the presence of rare, random, resistance-conferring genetic changes within tumor cell populations that are selected during drug treatment (Sharma et al., Cell 141(1):69-80 (2010)). A phenomenon that is increasingly observed in cancer therapy is the so-called "retreatment response". For example, some patients with non-small cell lung cancer (NSCLC) wh...

Claims

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Application Information

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IPC IPC(8): A61K45/06
CPCA61K45/06A61P35/00A61P35/04A61P43/00
Inventor D·拉哈J·赛特尔曼T·R·威尔逊
Owner F HOFFMANN LA ROCHE & CO AG
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