Cancer Awareness

At least one-third of all cancer deaths can be prevented through routine screening, early detection and treatment. More than 40% of cancer-related deaths are avoidable because they are linked to modifiable risk factors such as use of tobacco and alcohol, poor diet, and lack of exercise.

We wish to highlight some interesting facts about stem cells and cancer.

Cancer stem cells and tumour biology

Cancer stem cells (CSCs) are a particular type of tumour cell that can drastically influence the development and growth of cancer. Our knowledge of CSCs is important for treating cancer and improving cancer therapies. CSCs can self-regenerate and differentiate, and can potentially induce growth, and spread cancer in patients, which will often result in the recurrence of cancer in a patient.

The current aim of researchers is to find cancer drugs that can target and fight CSCs to treat cancer successfully.

Various approaches to target CSCs are being investigated, i.e., disrupting signaling pathways, targeting particular surface markers, or by using specific drugs; but all these methods are difficult because of genetic and epigenetic variation in patients, as well as sharing of similar pathways between normal stem cells and CSCs. Therefore, targeting CSCs remains restricted and at present is still a major challenge to scientists and researchers (1).

Stem cell innovations hold promise to improve cancer treatment.

Two new breakthroughs may help make cancer treatment more effective and reduce the time it takes for people to recuperate from radiation and chemotherapy.

Blood stem cells, like those found in the peripheral blood and bone marrow offer curative treatment in for instance leukaemia’s and lymphomas. However, this haematopoietic stem cell transplant (HSCT) method suffers from various problems, e.g., slow recovery, toxicity, degeneration of blood vessels and low blood counts. Scientists have found two recent technologies to overcome these challenges.

When bone marrow or peripheral blood transplants are done, these blood forming stem cells form only a small percentage of the cells that are transplanted. Thus, when people receive a transplant, these cells that must do the “work” are in the minority and the many other cells that do not help in regenerating the blood, are the majority of cells.

Scientists have now found a way to identify these cells and isolate them more efficiently. A protein called syndecan-2, occurs in high concentration on these haematopoietic stem cells’ surfaces. Blood stem cells that express syndecan-2 on their surface were able to repopulate and regenerate new blood cells, but those cells that lacked this protein, stopped replicating.

By using these syndecan-2 isolated cells, blood stem cell transplants will be more efficient and less toxic in future (2).

Another major discovery made during blood stem transplants; is where scientists discovered a protein that plays a significant role in killing damaged blood vessels in bone marrow after chemotherapy and radiation. This protein therefore plays a major role in bone marrow vasculature degeneration and the fall in blood counts after injury. Scientists found that by blocking this protein, called semaphorin 3A and its partner protein, neuropilin 1, that the blood vessels and blood cells in bone marrow rapidly regenerated and blood counts dramatically increased (3).

Therefore, by targeting this mechanism patients will recover quicker than with conventional methods.

Umbilical cord blood (UCB) is another source of autologous and allogeneic HSCT to treat various haematological disorders. The biggest restraint to using UCB-derived HSCs (UCB-HSCs), however, is the low numbers of HSCs in a unit of cord blood. In the past 5 to 10 years, scientists have overcome this by identifying various cytokines or small molecules to expand UCB-HSCs ex vivo (in culture). They found that various small molecules and combinations of small molecules can exert a cooperative effect and increase UCB-HSCs numbers and their transplantation outcomes (4).

New molecule produced by the human body can protect against Graft-versus-host disease (GvHD)

Acute Graft-versus-host disease (GvHD) is an aggressive complication after Leukemia or related cancer treatment with allogeneic (donor cells from another person) stem cell transplantation. GvHD occurs after transplantation when the immune cells are overly functional and harm the recipient’s healthy tissue. Researchers from Freiburg found that an endogenous molecule (produced in the human body) can relieve this harmful immune response. They found that giving human beta-defensin 2 (hBD-2) to mice with acute GvHD, significantly improved their GvHD and survival. Thus hBD-2 is now an interesting candidate for more studies and clinical trials and might be used as a preventative treatment in future allogeneic stem cell transplantation (5).

New Cancer vaccine that can kill and prevent brain cancer

A group of scientists at the Department of Neurosurgery at the Brigham and faculty at Harvard Medical School and Harvard Stem Cell Institute (HSCI) have developed a way to convert cancer cells them into cancer destroyers as well as vaccines. By gene engineering, they can repurpose cancer cells to develop a therapeutic that kills tumour cells and stimulates the immune system to both destroy primary tumours and prevent cancer. This two-fold cancer-killing and -prevention vaccine was tested in an advanced mouse model of the deadly brain cancer glioblastoma and will soon be tested in clinical trials (6).

These afore-mentioned research breakthroughs highlight the fact that further elucidation of the functioning of stem cells and their role in tumour biology is needed to continue developing new and innovative therapies for cancers.  

References

1. Yu Z, Pestell TG, Lisanti MP, Pestell RG. Cancer stem cells. Int J Biochem Cell Biol. 2012 Dec;44(12):2144-51. doi: 10.1016/j.biocel.2012.08.022. Epub 2012 Sep 2. PMID: 22981632; PMCID: PMC3496019.
2. Termini CM, Pang A, Li M, Fang T, Chang VY, Chute JP. Syndecan-2 enriches for hematopoietic stem cells and regulates stem cell repopulating capacity. Blood. 2022 Jan 13;139(2):188-204. doi: 10.1182/blood.2020010447. PMID: 34767029; PMCID: PMC8759530.
3. Ethan M. Lotz, Michael B. Berger, Barbara D. Boyan, Zvi Schwartz.Regulation of mesenchymal stem cell differentiation on microstructured titanium surfaces by semaphorin 3A. Bone. 2020; 134: 115260.
4. https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30202-9/fulltext
5. Tamina Rückert, et.al. Human β-defensin 2 ameliorates acute GVHD by limiting ileal neutrophil infiltration and restraining T cell receptor signaling. Science Translational Medicine, 2022; 14 (676).
6. Zhao, T., Li, C., Ge, H. et al. Glioblastoma vaccine tumor therapy research progress. Chin Neurosurg Jl 8, 2 (2022). https://doi.org/10.1186/s41016-021-00269-7.