On the Limitations of Standard-of-care and the Potential of Integrative Therapy

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Recently, there have been great advances in the fields of biology, with many technologies – like DNA editing, DNA and protein synthesis, and structural prediction – making huge progress.¹ Of course, these technologies have also found their way into cancer research, where they're allowing researchers to attain a better understanding of the mechanisms underlying the disease². However, despite these technical and scientific advances, standard therapy for cancer patients has remained relatively stagnant.

This doesn't mean that there has been no progress at all, with novel therapeutic approaches like immunotherapy, RNA therapies, more specific targeting of approved drugs, and other promising interventions being developed and seeing first clinical implementations. Still, these new treatments are often limited to a select set of treatable cancer, with specific genetic or molecular signatures that can be exploited. If a cancer doesn't happen to be one of the "treatable" cancers, patients are still stuck with the classical options of chemotherapy, radiotherapy, and surgery.³ In general, all treatments, new and old have the same goal of reducing tumour size.

Surgical approaches achieve this goal by physically removing the cancerous growth. In the optimal case, this can remove a tumour in its entirety without any side effects suffered by the patient. In practice, this however means that surgical approaches are really only viable, if tumours are discovered early on, and if they are accessible. If they are only accessible with significant risk to the patient or have spread to multiple sites, then surgery is no longer a viable option.

In that case the most common treatments are chemo- and radiotherapy. Both of these aim to reduce the size of the cancer by influencing the growth and death rates of cancer cells. The logic is, that if cancer cells die faster than they reproduce, the cancer will inevitably shrink. The problem with both of these therapies is that they are very poorly targeted. They are highly poisonous therapies that don't just act upon cancer cells, but also significantly damage and destroy healthy cells. The hope of these therapies is simply that the cancer cells will suffer more than the patient.^4,5

Because of this, chemo- and radiotherapy patients basically always suffer from side effects. Some of such side effects include things like nutrient depletion, hair loss, a collapse of immune cell populations – and therewith a suppression of immune function, which would ordinarily work to slow tumour growth –, and disruption of blood homeostasis – which has negative consequences for nutrient and oxygen distribution – to name a few.^6,7

I don't think it's necessary to say, that this isn't great. Beside significantly reducing the quality of life for cancer patients, this strain on the body also limits its innate ability to fight back. At some point, the body of the patient will be so ruined that treatment with chemo- or radiotherapy can no longer be continued due to side effects, which opens the door for cancer to potentially re-emerge.⁸

Holistic approaches

The goal of a holistic approach to cancer care must be to minimise the negative impact on patient quality of life, whilst also further diminishing cancer growth and spread, as well as dealing with the risk of cancer recurrence.

How on earth would one even do all these things at once? Seems complicated, right? It is, but let's take a look at it.

So, if we want to improve patient quality of life, there are two things we need to do. We need to help the body deal with the direct adverse effects of radio- and chemotherapy, but we also need to address the nutrient depletion often wrought by such therapies. Both of these approaches, naturally go hand in hand.

Minimising adverse effects

It is well known, that both chemo- and radiotherapy bring with them a high risk of adverse effects. A substantial portion of these are caused directly by the drugs damaging and killing non-malignant cells (healthy cells). Because chemo- and radiotherapeutic drugs are designed to target fast-growing cells, the direct side effects are often most severe in tissues with high cellular turnover. This is why balding is such a well-known indicator of chemotherapy.⁹ The cells of the hair follicles grow very quickly and are thus heavily affected by the drugs. Whilst balding is of course not desired, it is also one of the more benign side effects. Others, like reduced red blood cell counts or a collapse of the immune cell population can have much more dire consequences for patients.

Preventing damage to healthy tissues would greatly reduce the side effects suffered by patients undergoing treatments. However, because the underlying mechanisms that these therapies leverage are fundamentally not specific to cancer it's unlikely that this damage can be completely avoided, without stopping therapy.

Some compounds like curcumin, Cordyceps sinensis extract, and Ganoderma lucidum extract, which separately combat cancer growth through various mechanisms have been found by some studies to protect patients from the adverse effects of chemo- and radiotherapy.^10,11,12,13 However, the data on how reliably these compounds do this is rather heterogenous. The upside is that they generally have few side effects of their own, although there are some concerns with regard to their interactions with chemo- and radiotherapeutics.

For example, a review cautioned that curcumin can increase absorption and reduce clearance of some chemotherapy drugs. Curcumin also inhibits multiple CYP450 isoenzymes which can affect pharmacodynamics of co-administered drugs. Enzymes of the CYP450 family are used primarily in the liver to clear out foreign substances the body want to rid itself of, such as curcumin itself and of course chemotherapeutic drug. So, inhibiting CYP450 isoenzymes simply lowers the clearance speed of foreign substances, which can potentially endanger patient health and wellbeing.¹¹

Due to the heterogenous data on radio- and chemoprotection as well as uncertainty surrounding potential interactions it is difficult to provide blanket recommendations without considering the individual co-administered drugs. If you personally want our tailored help, or know someone who does, you can schedule a call with us at www.marchward.com/outlive.

Another group of side effects of chemo- and radiotherapy are nutrient deficiencies. Even in cancer patients not undergoing treatment, they are very prevalent. Exact numbers vary depending on detection methods, populations, and the definition of "deficiency" which is used. One study found vitamin D deficiency in 90% and vitamin B1 deficiency in 80% of cancer patients examined.¹⁴ A different study found severe malnutrition in 33.3%. Undergoing treatment seems to worsen the nutritional deterioration observed in cancer patients.¹⁵

Correcting for nutrient deficiencies would give the body what it needs to restore the tissues that are damaged by therapies and the cancer more effectively. It would also ensure that tissues, which aren't directly affected by either of the two, can continue to perform well.

One thing to note here is that both deficiencies and excessive levels can be detrimental. Thus, blanket high-dose supplementation isn't recommendable, because it can lead to excessive levels of nutrients. For many nutrients supplementation at low dosages is unlikely to cause any issues. However, there are also nutrients where the risk is higher.

How risky blind supplementation of a given nutrient is can be approximated by considering its therapeutic window. The therapeutic window refers to the distance between the dosages at which deficiency and toxicity occur. A bigger distance between these dosages, means that a nutrient has a bigger therapeutic window and is on average less risky. For example, Vitamin B12 has an RDA of around 2.4 µg/day, but it's toxicity is so low that there isn't even an established upper limit.¹⁶ In contrast vitamin A has an RDA between 700 and 900 µg/day but a recommended upper limit of 3000 µg/day.¹⁷ Of course, the upper limit is determined with some safety margin, but the effects of too much vitamin A are well-characterised.¹⁷

Without going into the therapeutic window and potential risks of every single nutrient, the safest approach is to simply perform nutrient screening through testing a blood sample. This allows for determination of specific deficient nutrients, which can then be followed up by selective supplementation of only the required nutrients. This way, over-supplementation of nutrients can be avoided and the risk of toxicity reduced. Follow-up screening to detect when a deficiency has been cleared up and to avoid over-correction is of course also recommendable.

Diminishing cancer growth and spread

In cancer care, a monotherapy is any treatment where only a single pharmaceutical is used. Compared to combination therapies which make use of multiple different drugs, monotherapies are more vulnerable to drug resistance and they are less able to cover tumour heterogeneity. Because of this, they generally provide worse disease control and their maximal effects are limited compared to combination therapies.¹⁸

Despite the potential upsides of combination therapies, monotherapies are still very common. Between 2011 and 2023 two thirds of the FDAs approval entries for tumour therapies were monotherapies.¹⁹ With respect to drugs approved within the European Union, there are no such clear numbers. One report by the EFPIA entitled "Access to Oncology Combination Therapies in Europe: Moving Forward" states that between 2015 and 2022, the EMA approved 35 novel combination therapies.²⁰ In a different report with the title "Comparator Report on Cancer in Europe 2025 - Disease Burden, Costs and Access to Medicines and Molecular Diagnostics" the EFPIA provides a graph (figure 49 in case you want to have a look yourself) summarising approvals of novel medicines since 1995.²¹ From this graph, it seems that between 2015 and 2022 90~100 new cancer medicines were approved.

This would mean that both in the US, as well as the EU, the fraction of combination therapies among novel approvals is only one third. One reason for the continued use of monotherapies is that, due to their simplicity, they are somewhat easier to predict and can be less toxic. Especially in the case of classical chemo or radio drugs their toxicity can stack when combined, leading to more severe side effects.

Furthermore, even when combination therapies are utilised, they often combine multiple classical drugs that all function by simply killing cancer cells faster than healthy tissue. However, if we look beyond the scope of classical cytotoxic drugs, research has shed light on a plethora of different interventions that have shown promising anti-cancer efficacy without incurring severe side effects.

Examples of these include, but are not limited to hydrogenated water, alkalisation therapy, ketogenic diet, DCA, and fenbendazole.^22–27

Now, I would love if I could simply give you a quick list like this, of what these interventions are, and then send you on your way. However, such a list would lack any of the necessary nuance and details surrounding the interventions, which would be indefensible. After all, we are still talking about cancer care. Even though these interventions generally don't cause severe side effects, they are still pharmaceutical interventions with complex ramifications. As such, each intervention requires consideration to ascertain its potential upsides and downsides, before its implementation should commence.

The benefit of such interventions is that they can be implemented, without adding further burden to the patients body. In some cases, like the previously mentioned curcumin or Ganoderma lucidum, there is also data that suggests they might not only be neutral towards adverse effects of classical therapies, but could even be protective against them.

The goal of a holistic approach to cancer care is to combine interventions in a way that achieves strong anti-cancer effects, whilst improving patient quality of life.

Dealing with cancer recurrence

Dealing with cancer recurrence is closely linked to both minimising the adverse effects suffered during treatment, as well as implementing different interventions to diminish growth and spread. To understand why this is the case we have to first take a look at why recurrence of a cancer is such a significant obstacle to cancer treatments in the first place.

The main reason that recurrence occurs even after seemingly complete remission is that even the most effective cancer treatments rarely – if ever – manage to eradicate all cancer cells in the body.^28,29 So, even when patients are declared "cancer-free", it's very likely that they aren't actually cancer-free, but that instead the cancer has simply shrunk to an undetectably small size.

The surviving cancer cells are usually those that have adapted to the pressure that therapy has placed upon them. Since classical therapies especially affect rapidly dividing cells, those cells, which persist, tend to be quiescent cells. Quiescence is a state, in which cells are not actively multiplying. This means, that despite these quiescent cancer cells still being fundamentally cancer cells, they exhibit different cellular properties from normal cancer cells and grow much more slowly, if at all. This drastically reduces the efficacy of cytotoxic treatments such as chemo- and radiotherapy and makes them largely invisible to the most wide-spread imaging methods used nowadays.^30,31

Now, we have already talked about the side effects, which accompany classical treatments. Because of their severity, once a cancer shrinks to an undetectable level and complete remission is declared, treatment is usually suspended to protect the patient's body from further harm. However, this gap in treatment provides remnant cancer cells with temporary relief, during which they can reactivate and begin to grow once more.

If we want to prevent recurrence, there are two points at which we – in theory – can act. First, we could attempt to develop treatments, which achieve complete eradication even of quiescent cancer cells. If this were to be achieved, there would be no quiescent cells capable of reactivating and thus recurrence would become impossible. Whilst this idea is being explored in research, current approaches fail to achieve such therapeutic depth.

The second option is developing treatments which more effectively prevent quiescent cancer cells from reactivating. Even though this approach would fail to achieve a true cancer-free state, quiescent cancer cells do not pose any significant danger to the patient as long as they remain quiescent.

The downside to this approach is, of course, that the only way to reliably achieve this is to use perpetual treatment, that maintains pressure on cancer cells to retain their quiescent phenotype.

Maintaining chemo- or radiotherapy indefinitely is pretty much impossible for previously mentioned reasons. Whilst reducing the side effects suffered by these classical therapies is going to theoretically allow for longer treatments, it is unlikely that treatment can be extended indefinitely. So, even though reducing side effects would leave the patient's body less exhausted and thus more capable of fighting a potentially recurrent cancer on its own, it doesn't address cancer recurrence itself, as it helps neither with fully eradicating cancer cells nor with indefinitely perpetuating treatment.

Because of their lean side-effect profiles and modular nature the aforementioned adjuvant interventions can be maintained indefinitely much more easily. Say for example, a patient is taking a battery of 25 pharmaceutical interventions, and one of these turns out to be detrimental to the patient's health. Treatment wouldn't cease, but simply be adapted to that specific patient's needs.

Additionally, using multiple interventions which attack the cancer by different attack vectors tendentially allows for a greater reduction in cancer growth. It is also less likely that a cancer becomes simultaneously resistant to multiple different interventions, than it becoming resistant to only one drug.¹⁸

Closing remarks

And this brings us to the end of this article.

Despite significant advances in biology and medicinal research, the standard-of-care for cancer patients has remained largely the same and the benefits are concentrated on a subset of "treatable" cancers. When pursuing standard care, little has changed for a majority of patients and as a result they still have to deal with the severe side effects and high risk of recurrence that accompany these treatments.

Though this stagnation of standard cancer care is rather sad, there is hope in a holistic approach. Consciously screening for deficiencies and supplementing nutrients improves the quality of life for cancer patients whilst also potentially improving treatment efficiency. Furthermore, expanding beyond the simple cytotoxic drugs commonly used and integrating a battery of different interventions allows for the establishment of a treatment regime that is more modular and adaptable with fewer side effects. Such a modular regime is also much more easily maintained which helps with combating recurrence.

Though cancer remains a vicious disease, a holistic approach to cancer that considers all aspects of the patients life as well as treatment of his disease offers potential for much better patient outcomes.

And I'll leave you on that positive note.

I wish you a great day and swift healing.

Cheers,
Cedric

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