Drug repurposing in oncology—patient and health systems opportunities

Abstract

In most countries, healthcare service budgets are not likely to support the current explosion in the cost of new oncology drugs. Repurposing the large arsenal of approved, non-anticancer drugs is an attractive strategy to offer more-effective options to patients with cancer, and has the substantial advantages of cheaper, faster and safer preclinical and clinical validation protocols. The potential benefits are so relevant that funding of academically and/or independently driven preclinical and clinical research programmes should be considered at both national and international levels. To date, successes in oncology drug repurposing have been limited, despite strong evidence supporting the use of many different drugs. A lack of financial incentives for drug developers and limited drug development experience within the non-profit sector are key reasons for this lack of success. We discuss these issues and offer solutions to finally seize this opportunity in the interest of patients and societies, globally.

Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis

“…Newer ROCK inhibitors such as K-115 (Ripasudil), which have recently entered the clinic for the treatment of glaucoma (101,102) or are currently in the clinical testing pipeline, including phase 2 clinical trial for glaucoma (AMA0076) (103), or CCT129254 or AT13148, which reduce metastasis in other cancers (104), could also have similar applications (105). Patient presentation in PC ranges from early local invasion at the time of diagnosis to late metastatic disease (106).…”

Repurposing of Anthelminthics as Anticancer Drugs

“…Approval may be accelerated by knowledge of previous preclinical and clinical data on pharmacokinetics, side effects and regimens [5,87,88]. Anticancer activities of several anthelminthics attracted considerable interest, especially their capacity to target signal transduction pathways of CSCs/TICs of several tumor types.…”

“…The substituted quinoline pyrvinium pamoate (PPAM) is a cyanine dye which has been used to treat pinworm (Enterobius vermicularis) infections as well as strongyloidiasis in humans [5,27]. Pyrvinium exhibits a dark-red fluorescent color which yields a higher signal upon interaction with DNA [82,83].…”

“…Potential agents should possess anticancer activity at physiologically relevant doses, with low toxicity and, preferentially, at low cost [5]. Candidates may reveal another mode of action against cancer cells than in their original indication and require different concentrations to exhibit efficacy in antitumor regimens.…”

Inventing new therapies without reinventing the wheel: the power of drug repurposing

“…According to some estimates, the cost is only $40-80 million in total for FDA approval through the repurposing route, compared to the $1-2 billion it takes to develop a drug starting from hit selection in vitro. However, this figure for repositioning may be too optimistic as it does not take into consideration the costs of failed repurposing trials (Bertolini et al, 2015;Ishida et al, 2016;Cha et al, 2018). In the often-quoted figure of $1-2 billion as the cost of new drug development (see Tufts Center for the Study of Drug Development; http://csdd.tufts.…”