In December 2022, President Joe Biden signed a groundbreaking law permitting researchers to test drug candidates on human-based models or computer models before conducting human trials. This law has changed the long-standing requirement, dating back to the 1930s, that mandated drug and vaccine testing on both rodent and non-rodent species.
While this change encourages a reduction in animal testing, particularly in early-stage research, it underscores the need for researchers and funders to validate disease models – including cancer, based on humans.
Luckily, technological developments have already introduced significant scientific advancements in addressing many diseases through “Induced Pluripotent Stem Cells” (iPSCs).
What is iPSC?
According to the UCLA Broad Stem Cell Research Center, induced pluripotent stem cells “are derived from skin or blood cells that have been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes.”
In other words, since the developmental states, all of the body’s cells come from stem cells, which can become any cell type. This natural differentiation gave birth to the idea of “pluripotency.” Dr. Kazutoshi Takahashi and Dr. Shinya Yamanaka made this discovery in 2006. Since this discovery, iPSCs have been accepted as a revolution in the biomedical field by offering new opportunities for disease modeling, drug screening, and regenerative and personalized medicine.
Their application in cancer research holds significant potential for advancing the understanding and treatment of various cancers. Here, we willl delve into iPSCs in cancer research and therapies and lay the groundwork for further examinations of the topic in Breaking Cancer News.
The Potential of iPSCs in the Cancer Field
iPSCs are generated by reprogramming adult somatic cells –cells in the body that are not reproductive cells – such as skin cells. Reprogramming provides a “differentiation state” for these cells to become almost any cell type, called the “pluripotency.” By resetting the adult cells to stem cells with this approach, they become capable of differentiation.
Disease Modeling & Drug Screening
Dr. Mehdi Soleymani-Goloujeh from the University of California recently described the potential of iPSCs in a conversation with Breaking Cancer News.
“iPSCs are promising for creating personalized disease models that reflect the genetic and epigenetic traits of specific tumors in each patient. This enables us to explore the mechanisms behind cancer progression and identify targeted therapies tailored to individual patients. Patient-specific modeling and searching for the best strategy to battle the disease is the fascinating part of these cells.” he said.
iPSC-derived cancer models enable high-throughput screening of potential anticancer drugs. These models help identify compounds that are effective against specific cancer types. Additionally, this approach can be used to assess drug toxicity and side effects in the human model which relatively decreases the side effect risk.
Regenerative Medicine
Cancer treatments, such as chemotherapy and radiation, often cause significant damage to normal tissues. iPSC-derived cells can be used to regenerate and repair damaged tissues, improving the quality of life for cancer survivors. For example, iPSC-derived hematopoietic stem cells can help restore the bone marrow after aggressive cancer treatments.
Gene Editing
Combining iPSC technology with gene editing tools like CRISPR/Cas9 is another mind-blowing opportunity that iPSCs provide. It allows for correcting cancer-associated genetic mutations. This means that researchers can edit patient-derived iPSCs to repair mutations and then differentiate them into healthy cells for transplantation. This approach holds promise for curing cancers driven by specific genetic abnormalities.
Understanding Cancer Nature
In cancer biology, we also have “cancer stem cells.” They are tumor cells that contribute to tumor growth, recurrence, and resistance to treatment. Recent studies indicate that iPSCs can provide a unique platform to study “cancer stem cell” biology as well, since they share some key characteristics with cancer stem cells. With this approach, researchers can use iPSCs to deeply investigate the mechanisms of cancer stem cell maintenance, resistance, and targeted therapies.
Dr. Soleymani-Goloujeh also thinks that iPSCs can be used to study tumor micro-environment as differentiated into different cell types, including immune and stromal cells, which are essential for studying the tumor microenvironment.
“This leads us to understand how different cells interact with cancer cells and tumor microenvironments and influence tumor growth and progression,” he explained.
Personalized Medicine & Immunotherapy
“iPSCs highlight a novel approach to personalized medicine by creating patient-specific models to study cancer biology and examine different treatment strategies. This can proceed to more personalized and effective therapies according to the very specific genetic background of each patient and pave the way for precision medicine,” stated Dr. Soleymani-Goloujeh.
iPSCs can also be differentiated into immune cells and engineered to target cancer cells. This strategy offers a renewable source of immune cells for cancer immunotherapy. This is a promising approach as it may potentially overcome limitations associated with donor cell availability and variability.
Challenges and Future Directions
While iPSCs are promising for cancer research and therapy, several challenges still exist including safety and stability. As mentioned above, iPSCs share similar characteristics to cancer cells. Therefore, avoiding potential tumorigenicity and addressing ethical concerns about genetic manipulation is essential.
Additionally, translating iPSC-based therapies from the laboratory to the clinic requires rigorous testing and validation. However, with the help of technological development and future research, it is quite possible that iPSCs will become more common in the field.
When asked whether iPSC-based cancer therapies will be commonly used in the near future, Dr. Soleymani-Goloujeh replied, “As a scientist, I believe iPSC-based cancer therapies have great potential and could become more common very soon. When you have the option of differentiating them to different cell types they could be used for personalized, targeted treatments, such as creating patient-specific immune cells to attack cancer. While there are remaining challenges like safety and ethical concerns, the present ongoing studies and clinical trials are moving us forward to the broad use of iPSC-based therapies in cancer treatment.”
In conclusion, Dr. Soleymani-Goloujeh told Breaking Cancer News:
“iPSCs represent a transformative tool in cancer research and therapy. Their versatile usage allows us for a deeper understanding of cancer mechanisms and the development of personalized cancer therapies. As research continues to advance, I am very confident that these cells will become increasingly integral in offering more effective, precise, and low-cost cancer therapies, which ultimately improve patient outcomes.”
