Many types of treatment are available for cancer today. The choice of the most appropriate one, or combination of them, depends on the type of cancer a person has and how the disease is advanced.
Major treatment options include:
- the surgical removal of the tumor mass from the body;
- the local use of high doses of radiation to kill cancer cells and make the tumor mass smaller;
- the systemic use of drugs that may
- kill rapidly proliferating cells (chemotherapy),
- help the immune system to fight cancer cells (immunotherapy),
- target specific molecular traits of cancer cells that help them proliferate and spread (targeted therapy); or
- kill or impair cancer cell that depend on hormones for their growth (hormone therapy for breast and prostate cancer).
Despite the great advancements made in treating cancers during the past decades, however, the tolerance of cancer cells to classical chemotherapeutic treatments and/or last generation therapies still remains a major challenge.
The insensitivity of cancer cells to treatments can be a pre-existing property of a patient’s tumor or it can develop during the course of therapy. In both cases, it represents a major cause of tumor relapses and death of the disease.
Why do cancer cells resist?
Cancer drug resitance
To date, different factors have been associated with chemosensitivity and drug resistance of cancer cells.
Treatments with chemotherapy and targeted drugs can have reduced efficacy because of the presence of insensitive subpopulations of cancer cells, within the tumor mass, that are defined by pre-existing mutations in genes that are key to cancer cell growth and response to chemicals. Relevant genes are involved in controlling drug accumulation within the cell, the repair of DNA, or programs that control cell death.
Importantly, during drug treamtents new mutations or alteration in cancer cell gene expression can arise that cause the altered expression of different signaling pathways or the modification of drug targets. This can convert the originally treatable cancer cells into treatment resistant tumor cells.
Not only mutations but also other types of alterations affecting the so-called “packaging of DNA” into the ordered structures of chromatin, can contribute to the development of therapy resistance.
The tumor microenvironment
Moreover, tumors are made of not only cancer cells, but also the environment surrounding them with various types of cells including fibroblasts, immune, and inflammatory cells, as well as the extracellular matrix with collagen fibers, various signaling molecules, blood vessels and others, that can communicate with cancer cells and contribute in determining the response to therapy.
The stiffness of tumor microenvironment, for example, is associated with impaired drug distribution within the tumor mass, and with the activation of oncogenic signals that in turn have been shown to be associated with drug resistance.
The immune system has an intrinsic potential to constrain the development of tumor tissues by recognizing emerging cancer cells and operating their clearance. However, cancer cells can hide from the immune system by hijacking the immune checkpoints and favoring the establishment of an immunosuppressive microenvironment, that is known to enhance cancer development and cancer resistance to immunotherapies.