Portrait of cancer patient. Image source: vecteezy.com
Cancer remains the second leading cause of death worldwide. The Canadian Cancer Society estimates about 247,100 new cancer cases and 88,100 cancer deaths in Canada in 2024. Ten million deaths worldwide have been estimated to have been caused by cancer in 2020. This number is expected to be over 16 million in 2040 and includes a growing number of young people. Over the past three decades, there’s been a 79 per cent increase in new cancer diagnoses in people under the age of 50 and, this year alone, expectations for new cancer cases in the U.S. have crossed the two million threshold.
The staggering statistics underscore the urgency of finding more effective solutions than those already existing. This is because chemotherapy, radiation and surgery, while essential in the fight against cancer, often bring along a host of side effects that can be as debilitating as the disease itself. From “chemo brain” to nausea, hair loss and fertility issues, the toll it takes is immense. However, while novel solutions are in the works, and ongoing research has intensified, could the side effects of current solutions like chemotherapy be attenuated with regenerative medicine? Considering this potential, it’s essential to understand how these treatments impact patients on a physiological level.
How side effects of cancer treatment affect us
Chemotherapy and radiotherapy work by targeting rapidly dividing cells, including cancer cells. However, they also affect normal, healthy cells and can cause a significant decrease in the number of healthy red blood cells leading to anemia and symptoms associated with it, such as shortness of breath, fatigue, chest pain, tachycardia, pallor and light-headedness. Neutropenia and thrombocytopenia also arise, exposing the body to infections, easy bruising and bleeding manifesting as petechiae, nosebleeds and heavier menstruation.
Chemotherapy drugs can cause systemic toxicity, affecting organs such as the bone marrow, gastrointestinal tract and hair follicles. Ovarian failure resulting in sexual dysfunction and infertility, neurotoxicity and neurocognitive decline, are some of its affectations. In the same vein, radiotherapy damages both cancerous and non-cancerous tissues within the irradiated field, leading to inflammation, fibrosis and impaired wound healing.
Long term, chemo and radiotherapy are capable of damaging the heart, liver and kidneys, giving rise to different cardiomyopathies, as well as liver and kidney failure. Following radiation 40 per cent of patients suffer from radiation mucositis characterized by inflammation and immense pain when eating and talking. Radiation in the case of head cancer also causes alopecia (hair loss) alongside the psychological effects that come with it.
How we can alleviate side effects
The synergy of regenerative medicine and advanced technology now offers a glimmer of hope, promising a future where all the side effects of chemotherapy, radiation and surgery may become significantly reduced, making the process of cancer treatment gentler and more patient-friendly.
The regenerative medicine approach involves tissue restoration after death, or regrowth after damage.
How stem cell therapy has been used in combating the side effects of chemotherapy and radiotherapy
Stem cell research application in cancer therapy has been in practice for decades. The insufficient and non-specific approach at the beginning of its application has given way to new and improved discoveries that have transformed cancer care in the past decade. There is still a lot of work to be done but there is an increase in the number of recorded successes using stem cell therapy in cancer management.
This approach to combating the side effects of chemotherapy and radiation is grounded in the self-renewing, differentiating and modulatory effects of stem cells in the human body. Top on the list is its ability to boost the immune system, which is destroyed during chemotherapy and radiation therapy. In addition, stem cell therapy can improve the therapeutic efficacy of other cancer therapies by focusing on tumour targets and reducing the damage to healthy cells.
Stem cells have been widely studied and can be roughly categorized into several groups: embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and cancer stem cells (CSCs).
Mesenchymal stem cells (MSCs), a type of adult stem cell, have anti-inflammatory and immunomodulatory properties to help fight cancer, which can attenuate tissue damage and promote tissue regeneration. MSCs have been investigated for their potential to mitigate radiation-induced injury to organs such as the lungs, intestines and skin. Similarly, hematopoietic stem cell transplantation (HSCT) has been used to restore bone marrow function following chemotherapy-induced myelosuppression, thereby reducing the risk of infections and bleeding complications.
Regenerative medicine in the treatment of alopecia
Alopecia is one of the most conspicuous side effects of cancer treatment. Persistent or permanent alopecia is reported in 60 per cent of patients undergoing head and neck radiation therapy, 14 per cent of childhood cancer survivors and 30 per cent of breast cancer survivors. Scalp cooling is the number one preventative measure during cancer treatment, but regaining hair growth after persistent alopecia is possible with regenerative medicine.
A 36-year-old woman with chemo-induced complete alopecia from the treatment of an invasive ductal carcinoma received subcutaneous scalp injections of MSC-derived enriched vesicles. Three months after treatment, she presented with a full regrowth of terminal hair after having had no regrowth besides some light vellus hairs on her scalp before the treatment.
How it can be used in immunotherapy to avoid type 1 diabetes side effects
Immune checkpoint inhibitors work by circumventing T-cell inhibition. This process is used by tumour cells to evade recognition and destruction by upregulating factors in the cell signaling pathway. Type 1 diabetes can develop as an autoimmune side effect, along with a host of other issues. Conventional strategies to cure type 1 diabetes, once it develops, are currently unavailable; however, researchers at Osaka University have successfully used MSC therapy to block the onset of type 1 diabetes in mouse models. A study, led by Emi Kawada-Horitani, observed a significant reduction in diabetes incidence when MSCs were administered alongside the anti-PD-L1 antibody, compared to antibody-only treatment.
The research also brought to light the ability of MSCs to secrete protective pancreatic exosomes, protecting the pancreas of patients from further immune attacks and diabetes associated with immune checkpoint cancer therapy.
Using MSCs via a regenerative approach, the immune system can be modulated and restructured to normalcy. Visit Vertex Pharmaceuticals and Sernova Corporation for alternative ways of treating type 1 diabetes using regenerative medicine.
Management of neurologic side effects with regenerative medicine
Chemotherapy-Induced Peripheral Neuropathy(CIPN) and cognitive dysfunction (chemo brain)
Stem cells possess the remarkable ability to transform into nerve cells, offering hope for patients suffering from neuropathic pain due to chemotherapy or radiotherapy. Moreover, they can facilitate nerve regeneration by repairing damaged myelin sheaths and promoting angiogenesis, ultimately leading to lasting relief and recovery for peripheral nerve injuries. MSCs have been shown to have significant effects in decreasing oxidative stress, inflammation in the nervous system, cell death, and promoting the regrowth of nerve fibres following injury in various laboratory investigations and several medical trials.
In this study, nasal administration of MSCs was seen to reverse chemotherapy-induced peripheral neuropathy in mice.
In another study, intrahippocampal human neural stem cell transplantation also resolved chemotherapy-induced cognitive dysfunction in preclinical models. Eight per cent of the grafted cells survived and differentiated giving rise to neuroglia and astroglial cells that reduced inflammation and enhanced host dendritic arborization.
The regenerative medicine approach to combating the side effects of chemotherapy and radiotherapy is very promising, but more exciting is the hope for a cure, a hope whose flames are burning brighter now more than ever, especially following the successful applications of stem cell therapy in leukemia patients.
Future of regenerative medicine in cancer treatment
Connor Johnson survived acute myeloid leukemia with regenerative medicine. He’d already had two months of chemotherapy that was fruitless because of a mutation in his leukemia cells. He decided to sign up for a clinical trial at the MD Anderson Cancer Center, University of Texas. The treatment plan involved high-dose chemotherapy for a week followed by a two-day recovery period before a donor stem cell transplant. He spent an additional three weeks in the hospital post-transplant to reduce the risk of infection while his bone marrow was making new white blood cells and rebuilding his immune system. A cyclophosphamide prescription helped prevent graft vs host disease. He’s currently thriving and cancer-free as a result of the treatment.
Stem cell transplantation is currently a specialized treatment protocol for high-risk blood cancers, autoimmune disorders or patients who do not respond to treatment due to one or more complications. The high-dose chemotherapy kills resistant cancer cells and the stem cell transplant replaces the lost stem cells. Healthy stem cells introduced in the body produce new red blood cells, white blood cells and platelets, restoring the haematopoietic and immune system to a normal, cancer-free state.
So far, regenerative medicine has continued to progress towards more advanced and effective therapies in cancer management. As we continue to explore and refine these applications, we move closer to realizing a future where cancer can be managed and cured with greater precision and efficacy.
Peace Chukwu
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