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Repurposed Drugs for Cancer
Also Known As:
Off-label drugs, drug repositioning, repurposed drugs, drug repurposing, off-patent drugs
Summary:

Cancer cells require a tremendous amount of three fuel sources in order to survive: glucose, glutamine (an amino acid), and lipids. Mainstream medicine ignores this simple fact, focusing instead on using chemotherapy and radiation therapy to target the tumour’s abnormal, fast-dividing cells. There is well-researched evidence available showing the efficacy of attacking cancer from two fronts; starving the cancer’s stem cells and then killing them when they’re in a weakened state.

There are numerous drugs on the market designed for other purposes such as heart disease or infections that can be used as and adjunct or alternative to diet and supplements to effectively cut off cancer’s various fuel lines. These drugs are considered “off-label” or repurposed since they were developed for conditions other than cancer.

Drug repurposing is best defined as a strategy for identifying new uses for approved drugs, outside the scope of the original indication. It is a process of identifying new therapeutic use for old/existing/available drugs. This is an effective strategy in discovering or developing drug molecules with new pharmacological/therapeutic indications. Common examples include statins, angiotensin-receptor blockers, metformin, aspirin and vitamin D.

These “non-standard” options have become very common in cancer treatment – outside of conventional care – as they may improve standard treatment outcomes, reducing cancer risk or managing side effects, improve survival and reduce the risk of recurrence.

If you choose to explore these therapies, it is strongly recommended to seek guidance from a qualified professional who can help you choose the off-label and other novel therapies that are right for you and that are safe to use with your other therapies. Some of these therapies are readily available at low cost, but others may involve considerable expense and perhaps travel for access.

Description:

It is an emerging strategy where existing medicines, having already been tested safe in humans, are redirected based on a valid target molecule to combat particularly rare, difficult-to-treat diseases and neglected diseases.

This approach involves the strategic use of off-label drugs, including metformin, statins, and repurposed antibiotics, to disrupt the metabolic processes that fuel cancer growth. The approach focuses on targeting the metabolic vulnerabilities of cancer cells through a combination of repurposed medications, and aims to starve cancer cells of the nutrients they need to thrive while enhancing the effectiveness of standard treatments.

For example, Metformin (Glucophage), an oral anti-diabetic medication used widely in type 2 diabetes mellitus has been developed as a cancer therapeutic and is currently under phase II/phase III clinical trials. Aspirin has been traditionally used in the treatment of various pain and inflammatory disorders. It is also used in the treatment of heart attacks and strokes, and its usage in the treatment of prostate cancer has also been reported.

Thalidomide and its derivatives, which were developed to treat diseases such as psoriasis and inflammation related to infections, now play a role in many cancer therapies, both for their tumour growth inhibition and their anti-inflammatory activities. The earliest introduction of thalidomide derivatives to cancer therapy was to control inflammation. Eventually, their ability to prevent the growth of certain cancer cells was recognised.

Oncologists are also combining chemotherapeutics with compounds to control their effects on normal cells or improve their overall activity and repurposing drugs to control the effects of or enhance chemotherapy.

References show that the pantheon of approved drugs is a rich source of solutions for many problems in oncology. The pace of research on repurposing compounds from all clinical areas is breathtaking and has contributed to increasing survival and easing the effects of chemotherapy on cancer patients. In the proper settings, established drugs can be smart therapies that can replace untargeted toxins relied upon in the past.

Other protocols include usage of four commonly prescribed medications; metformin, atorvastatin, doxycycline, and mebendazole, in the effective treatment of glioma tumours, the most common type of brain tumour. These four drugs were selected for their evidence of efficacy, their synergy and their low side-effect profile.

Drug discovery and development remains a complex and time-consuming process, often hindered by high costs and low success rates. In the big data era, artificial intelligence (AI) has emerged as a promising tool to accelerate and optimise these processes, particularly in the field of oncology. In the field of tumour drug repurposing, AI models based on a large number of small molecule databases promote the discovery of anticancer uses of nontumour drugs. For instance, Corsello et al. created a molecular barcoding technology, which has become a public resource for drug screening using PRISM, containing 4518 drug growth inhibition activities in 578 human cancer cell lines.

Common off-label (repurposed) drugs used in cancer treatment are:

1) Statins

Satins are cholesterol-lowering drugs used to reduce mortality and illness for people at risk of cardiovascular disease. A secondary relationship between statins and cancer is being researched, as statins may have inhibitory effects on tumour growth, promoting cell death and preventing metastasis.

Statins, read more on CancerChoices 

2) Metformin

Also known as: Axpinet, Diagemet, Glucient, Glucophage, Metabet

Metformin is a drug predominantly used to treat type 2 diabetes. Evidence suggests that metformin is effective in reducing insulin and glucose levels in people with cancer. Moreover, people with type 2 diabetes have an increased risk of cancer, thus treatment with metformin of diabetes may help reduce cancer risk through reducing the cancer-promoting effects of type two diabetes. There is also some evidence that suggests metformin may improve cancer-specific mortality and tumour proliferation for certain patients. More recently, there is renewed interested in metformin in the field of ‘healthy-ageing’ to treat a range of age-related conditions.

Metformin, read more on CancerChoices 

3) Low-dose naltrexone (LDN)

Also known as: Revia, Vivitrol

LDN is an opioid antagonist, meaning it can be used to inhibit the action of opioids. LDN is normally used to treat addiction, and it has been suggested that a much lower dosage may be useful in treating cancer and other diseases. LDN may interfere with tumour growth by affecting cell signalling and the immune system. Preliminary studies suggest that LDN treatment may be promising for primary cancer patients, and more broadly may reduce inflammation and lessen pain.

How can low dose naltrexone help me, read more on CancerChoices

History:

Drug repurposing for cancer treatment has a history rooted in serendipitous discoveries and evolving understanding of disease mechanisms. Early examples, like the first chemotherapy drugs developed from mustard gas, demonstrate the concept of using existing compounds for new therapeutic applications. More recently, interest in repurposing has increased due to factors like the high cost and lengthy development time of novel drugs.

As our understanding of cancer biology has deepened, scientists have identified potential targets for repurposing drugs. For example, drugs that target metabolic pathways in cancer cells have emerged as promising candidates. Computational approaches, like machine learning and artificial intelligence, are being used to predict which drugs might be effective against specific cancer types.

Repurposing existing therapies and treatments provides an opportunity to capitalise well-characterised drugs that could synergise with existing therapies. Drug repurposing has gained popularity as a strategy to accelerate drug development because approved drugs have been already assessed for safety and efficacy, and therefore the risk of failure, timeframe, and overall costs from bench to bedside are considered to be lower than if a new or previously untested drug were being tested.

Given the high attrition rates, substantial costs and slow pace of new drug discovery and development, repurposing of ‘old’ drugs to treat both common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked compounds, with potentially lower overall development costs and shorter development timelines.

In traditional new drug development, it is estimated that 10–16 years are spent for the development of a new drug, while in repurposed drugs, the estimated time is between 3 and 12 years. It only costs $1.6 billion to develop a new drug using a drug repositioning strategy, while the drug development through traditional strategy costs around $12 billion.

In recent years, many pharmaceutical companies are developing new drugs with the discovery of novel biological targets by applying the drug repositioning strategy in drug discovery and development programme. This strategy is highly efficient, time saving, low-cost and minimum risk of failure. It maximises the therapeutic value of a drug and consequently increases the success rate. Thus, drug repositioning is an effective alternative approach to traditional drug discovery process.

However, off-patent drug repurposing has not always been a popular choice in the pharmaceutical industry as it offers a cheap and effective treatment without the huge profits of novelty drugs development. In 2015, Alistair Burt, the UK government health minister of the time deliberately blocked a new law to provide cheap and effective drugs for the NHS by championing medicines whose patents have expired. The Bill would have encouraged doctors to prescribe more off-patent medicines. Since the drugs are off-patent, the profit margins are lower, and generic manufacturers are reluctant to pay for the re-licensing process. While the Bill had broad support, it ultimately failed to pass, indicating the complexities of balancing public health concerns with pharmaceutical industry interests. (UK Health Minister Filibusters Bill To Use Off-Patent Drugs To Provide Effective New Treatments At Low Cost, techdirt.com)

The major driver of interest in repurposing is the public, spearheaded by Jane McLelland who has since inspired a raft of integrative practitioners to engage in the use of off labels alongside their other metabolic approaches. Many of the pathways targeted by off-labels can also be targeted with nutraceuticals, and practitioners are often combining both in their protocols.

Notes:

Listen to the Yes to Life Radio Shows Featuring This Therapy:

Science:

Sources:

  • Murray, Joseph C. MD, PhD; Levy, Benjamin MD Repurposed Drugs Trials by Cancer Type, The Cancer Journal: 3/4 2019 – Volume 25 – Issue 2 – p 127-133 doi: 10.1097/PPO.0000000000000371)
  • Gauthier Bouche, Craig Gedye, Lydie Meheus, Pan Pantziarka, Drug repurposing in oncology, The Lancet Oncology, Volume 21, Issue 12, 2020, Page e542, ISSN 1470-2045, https://doi.org/10.1016/S1470-2045(20)30561-1.
  • Maria Frantzi, Agnieszka Latosinska, Marika Mokou, Harald Mischak, Antonia Vlahou, Drug repurposing in oncology, The Lancet Oncology, Volume 21, Issue 12, 2020, Page e543, ISSN 1470-2045, https://doi.org/10.1016/S1470-2045(20)30610-0.
  • Pushpakom, S., Iorio, F., Eyers, P. et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov 18, 41–58 (2019). https://doi.org/10.1038/nrd.2018.168
  • Rudrapal, M., Khairnar, S. J. , Jadhav, A. G. , 2020, ‘Drug Repurposing (DR): An Emerging Approach in Drug Discovery’, in F. A. Badria (ed.), Drug Repurposing – Hypothesis, Molecular Aspects and Therapeutic Applications, IntechOpen, London. 10.5772/intechopen.93193.
  • Catherine H Schein, Repurposing approved drugs for cancer therapy, British Medical Bulletin, Volume 137, Issue 1, March 2021, Pages 13–27, https://doi.org/10.1093/bmb/ldaa045
  • Pérez-Plasencia Carlos, Padilla-Benavides Teresita, López-Urrutia Eduardo, Campos-Parra Alma D., Editorial: Repurposed Drugs Targeting Cancer Signaling Pathways: Clinical Insights to Improve Oncologic Therapies, Frontiers in Oncology, 11, 2021 https://www.frontiersin.org/article/10.3389/fonc.2021.713040 DOI=10.3389/fonc.2021.713040 , ISSN=2234-943X
  • Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling
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Last Updated:24/09/2023
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