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New Dimension of Glucocorticoids in Cancer Treatment

New Dimension of Glucocorticoids in Cancer Treatment


Glucocorticoids are frequently used in conjunction with other medications to treat cancer despite their unknown mechanism. They are helpful in the primary combination chemotherapy treatment of both acute and chronic lymphocytic leukaemias, Hodgkin’s and non-lymphomas, Hodgkin’s multiple myeloma, and breast cancer. Other applications for glucocorticoids in cancer patients include anti-inflammatory effects for cranial and spinal metastasis oedema, a modest antihyperglycaemic impact, and the capacity to control tumour-related fever.

What are glucocorticoid?

Glucocorticoids are hormones generated in the adrenal cortex and secreted into the bloodstream, where their levels change daily. Glucocorticoids are potent anti-inflammatory medications that act with your immune system to address a wide range of health issues. These hormones perform various functions, including regulating how your cells use sugar and fat and reducing inflammation. However, they are not always sufficient. That is where the artificial versions come in handy. Glucocorticoid medicines are synthetic copies of glucocorticoids, which are naturally occurring steroids in your body. They serve a variety of purposes. One method is to stop inflammation by going inside cells and inhibiting the proteins that cause inflammation. They also assist your body in responding to stress and regulating how it uses fat and sugar.

Type of Glucocorticoids

Steroids are naturally produced at modest levels by our bodies. They aid in regulating several activities, including the immune system, inflammation reduction, and blood pressure control.

Artificial steroids can also be used to treat a wide range of illnesses and disorders. Corticosteroids are a type of steroid that you may be given as part of your cancer therapy. These are synthetic replicas of the hormones generated by the adrenal glands, which are located directly above the kidneys(Lin, K. T., & Wang, L. H. (2016).

Steroids used in cancer treatment include:

  • Prednisolone
  • Methylprednisolone
  • Dexamethasone
  • Hydrocortisone

Why are steroids used in the treatment of cancer?

Steroids may be used as part of your cancer treatment for a variety of reasons. They can:

1. Deal with cancer itself

2. Lessen inflammation

3. Suppress your immunological response, such as after a bone marrow transplant

4. Aid in the reduction of illness after undergoing chemotherapy

5. Enhance your appetite

The following are some of the most common:

Cortisone – An injection that can reduce joint inflammation.

Prednisone and Dexamethasone – Medications used to treat allergies, arthritis, asthma, eye issues, and various other disorders.

Triamcinolone – A lotion that is used to treat skin problems.

Budesonide – A medication used to treat ulcerative colitis and Crohn’s disease, both of which are autoimmune disorders that affect the digestive tract.


In cancer therapy, glucocorticoids can be used to alleviate some of the adverse effects of chemotherapy. They may also be employed to kill cancer cells in some malignancies, such as:

1. Acute lymphoblastic leukaemia is a type of leukaemia that occurs in children.

2. CLL is an abbreviation for chronic lymphoblastic leukaemia.

3. Hodgkin lymphoma is a type of cancer that affects the lymphatic system.

4. Non-Hodgkin lymphoma is a type of cancer that does not originate in the body.

Glucocorticoids receptor:

Natural glucocorticoids (G.C.s), named after their role in glucose regulation, are cholesterol-derived hormones secreted by the adrenal glands. Immunological reactions, metabolism, cell growth, development, and reproduction all rely on G.C. circulation. In cells, the G.R. modulates the effects of G.C.s. It is a 97 kDa protein that belongs to the nuclear receptor superfamily of transcription factors (T.F.s) and is constitutively and ubiquitously produced throughout the body. Despite this, G.C.s have cellular and tissue-specific effects due to the presence of various G.R. isoforms on one hand and cell- and context-specific allosteric signals regulating G.R. action on the other. The GR regulates the expression of G.C. sensitive genes in either a positive or negative manner. It is estimated that 1,000 to 2,000 genes are susceptible to GR-mediated regulation, with some studies claiming that up to 20% of all genes are responsive to the G.R. in some form (Pufall M. A. (2015).

Natural glucocorticoids (G.C.s), so-called because of their function in glucose homeostasis, are cholesterol-derived hormones released by the adrenal glands. The circulation of G.C.s plays systemic processes in immunological responses, metabolism, cell growth, development, and reproduction(Strehl et al., 2019).

Inflammation and Glucocoticoids

G.C.s was initially recognised as effective anti-inflammatory medicines in the 1940s when Philip Hench successfully treated rheumatoid arthritis with G.C.s, for which he was awarded the Nobel Prize in 1950. Since then, both natural and synthetic G.C.s have been the most often prescribed immune suppressant drugs globally. G.C.s exert their anti-inflammatory effects via interacting with practically all resistant system cell types. Acutely, G.C.s reduce leukocyte recruitment by inhibiting vascular permeability caused by inflammation. They stimulate immune cells via inducing apoptosis, modifying differentiation fate, inhibiting cytokine production, inhibiting migration, and other mechanisms(Coleman, 1992).

Glucocorticoid in Cancer therapy

For nearly 70 years, clinicians have relied on G.C.s to treat lymphoid hematopoietic malignancies. Synthetic G.C.s, such as dexamethasone (DEX), are routinely included in all chemotherapy protocols to induce cell apoptosis in malignant lymphoid cancers like acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), Hodgkin’s lymphoma (H.L.), and non-Hodgkin lymphoma (NHL). Apoptosis caused by G.C.s appears to be a complex process involving numerous signalling channels. Transactivation of apoptosis-inducing genes such as Bim and negative regulation of survival cytokines via transrepression mechanisms, globally resistant, including suppression of AP-1 and NF-B mediated transcriptions. G.C.s monotherapy or combined therapy with other cytotoxic medications, such as 5-fluorouracil (5-FU), have shown modest effect in breast and prostate malignancies but not indifferent cancer types. The addition of G.C.s to other therapies, on the other hand, had no impact on long-term survival in advanced breast cancer(Caldwell et al., 2016)(Timmermans et al., 2019). Little is known about the molecular mechanism underlying the effects of G.C.s in breast and prostate cancer advancement. In addition to their usage as therapeutic reagents, G.C.s are generally acknowledged as an adjuvant during chemotherapy or radiotherapy to reduce adverse effects in various cancer types. Treatment for G.C.s promotes appetite, decreases weight loss, decreases fatigue, minimises ureteric obstruction, and prevents vomiting. G.C.s are sometimes utilised in the treatment of advanced cancer to lessen side effects for general palliative care.

Preclinical evidence

Despite an insufficient understanding of the underlying mechanism, G.C.s therapies have demonstrated minor improvements in patient survival in endocrine-responsive malignancies such as breast and prostate cancer. Preclinical evidence suggests that G.R. activation may reduce estrogen-induced cell proliferation in ER-positive breast cancer and attenuate androgen-activated A.R. gene expression in AR-active prostate cancer, implying that G.R. may cooperate with the other nuclear hormone receptors-ER and AR-to suppress this endocrine-responsive tumour growth.

Cancer metastasis is responsible for most of thereof endocrine-responsive tumour growth cancer-related mortality, yet the involvement of G.C.s in cancer metastasis has received less attention. In vitro cell models have revealed that G.C.s suppress cell migration/invasion via various mechanisms, including the down-regulation of RhoA [34], MMP2/9, and IL-6, and the activation of E-Cadherin. It also supports the growth of blood vessels. An animal model [29] indicated that therapy with T.A. reduced capsular thickness of the tumour, minor mononuclear inflammation, and negative or low angiogenesis in rabbits with breast cancer. According to Flaherty’s research, G.C.s can induce DNA damage via an inducible nitric oxide synthase (iNOS)-mediated route by increasing nitric oxide levels (NO); increased NO further driven by G.C. signalling may contribute to enhance angiogenesis via VEGF in a chronic stress scenario.

In prostate cancer, Yano et al. revealed that G.C.s acted directly through G.R. and suppressed two major angiogenic factors, VEGF and IL-8, in the androgen-independent prostate cancer cell line DU145. Additionally, in a xenograft model, except for intratumor VEGF and IL-8 gene expression, DEX treatment also inhibited angiogenesis and in vivo tumour growth [31]. Nevertheless, evidence exists that the G.C. signalling pathway can increase the diameter of blood vessels and vessel area in tumour tissues from prostate cancer patients.Ishiguro et al. [33] shown that DEX and PRED could inhibit the production of MMP-9, VEGF, and IL-6 in UMUC3 and TCC-SUP human urothelial carcinoma cell lines in bladder cancer. Another study looked at the effects of DEX on cell proliferation, apoptosis, and invasion in bladder cancer cell lines and discovered that, while DEX inhibited cell invasion and the production of angiogenesis-related genes (MMP-2/MMP-9, IL-6, and VEGF), it also caused cell death. mesenchymal-to-epithelial transition, it also correlated positively with cell proliferation in mouse xenograft models and resulted in a significant reduction in the curative effects of cisplatin

Cancer metastasis is responsible for most cancer-related mortality, yet the involvement of G.C.s in cancer metastasis has received less attention. In vitro cell models have revealed that G.C.s suppress cell migration/invasion by various mechanisms, including down-regulation of RhoA, MMP2/9, and IL-6, or by activation of E-Cadherin.

The significance of glucocorticoid signalling in non-hematologic malignant tumour growth and metastasis

In non-hematologic cancers, whether the action of G.C.s promotes or inhibits tumour growth is debatable. Previous research studies have shown that G.C.s can inhibit tumour growth and metastasis. Other studies have found that G.C.s reduce chemotherapy-induced cell death. A variety of cancers could cause this contentious phenomenon. subtypes, varying G.R. levels, and the quantity of G.C.s administered 

Brain and spinal metastasis

Brain oedema surrounding a tumour is caused by the breakdown of the blood-brain barrier (BBB) and leakage of plasma components from the blood. The typically tight intercellular connections are broken, and fenestrations form in the walls of tumour capillaries. The transport of water and solutes from the blood vessel lumen into the brain parenchyma causes ischaemia and inhibits neuronal function. Glial uptake of extracellular protein and transfer of extracellular fluid through a pressure gradient into the cerebrospinal fluid result in the resolution of cerebral oedema (CSF) . A range of therapies, including hyperosmolar solutions of urea, 42 glycerol, and mannitol, have been employed to assist this. Glucocorticoids, on the other hand, can either decrease oedema production or increase oedema reabsorption. The fact that glucocorticoids reduce tumour capillary permeability, induce anti-inflammatory effects by reducing oxygen free radical activity, and favourably affect the passage of salt and water across endothelial cells provides evidence for the latter.

Adverse Reactions

The way glucocorticoids impact you will vary depending on the medicine or the dose you take. For example, if you take one now and then for joint inflammation flare-ups, you may not have any adverse effects.

Steroids can mask or alter the signs and symptoms of certain infections. They may also make it more difficult for your body to fight infection. As a result, conditions are more challenging to detect at an early stage.

A change in temperature, aching muscles, headaches, feeling chilly and shivery, and feeling generally unwell are all symptoms of an infection. While using steroids, the patients may feel more worried and emotional than usual. You may also feel tired and unhappy when you stop taking them for a period.

When taking steroids, up to 6 out of 100 persons (6 per cent  ) have significant mental health difficulties. Depression is included. 

The following are examples of common problems:

  • Increased body weight
  • Swelling or water retention
  • Swings in the mood
  • Vision haziness
  • Sleeping difficulty

Blood sugar fluctuations

You may be subjected to regular blood and urine tests to monitor this. Diabetes affects some people. You may require blood sugar lowering medication. However, your blood sugar levels usually return to normal shortly after you stop using steroids.

If you already have diabetes, you may need to monitor your blood sugar levels more frequently than usual.

Weight gain and increased hunger

Steroids can make you hungry. Feeling hungry can make it challenging to maintain a healthy weight. When you stop using steroids, your appetite will return to normal, but some people will need to diet to shed the extra weight.

Consult your nurse or a dietician about how to maintain a healthy weight.


G.C.s are often utilised in cancer patients for various objectives and are the first line of defence in the treatment of inflammation and chronic inflammatory illnesses. However, the topic of how G.C.s function in tumour growth remains unanswered. In certain cancer types, G.C.s treatment may promote malignant solid tumours; nevertheless, it may also play a role in the progression of malignant solid tumours. For treating lymphocytic malignancy, almost all patients are given synthetic G.C.s 50–100 mg daily[28]; for relieving chemotherapy-induced nausea and vomiting, the dose of synthetic G.C.s varies from 8 to 20 mg[28]; and for inducing genes or microRNAs in mouse xenograft models, the human equivalent dose of synthetic G.C.s used can be as low as 0.1–03 mg Future research is needed to determine the ideal time, duration, and dosage of G.C.s, as well as the selection of relevant G.C.s among different cancer subtypes, to build a personalised strategy to match each individual’s needs.


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