The researchers of a new review have examined the relationship between cellular senescence and bone marrow cancers, looking at how senescence can ultimately fuel cancer development and how malignant cells induce senescence .
Senescent cells and cancer
As we get older, an increasing number of our cells enter into a state known as senescence, a state in which they no longer divide or support their tissues. Cells become senescent in response to various conditions and stimuli; in replicative senescence, they simply reach their replication limit (the Hayflick limit) and shut down, but damage can also trigger cells to enter this state.
Normally, senescent cells only last a short time and are quickly removed by the immune system, or they kill themselves via a process known as apoptosis, a kind of self-destruct sequence. Sometimes, cells become senescent on purpose in order to help facilitate wound healing, and in small, short-term doses, senescent cells are useful in this.
Cellular senescence is also thought to serve as a safety mechanism against cancer, preventing cells with potentially dangerous levels of DNA damage from replicating and removing them from the system. However, the problems begin when these cells are allowed to linger.
As we age, more and more cells become senescent and evade apoptosis and the immune system, and they remain at large in the body, causing all kinds of mischief. Senescent cells secrete a variety of harmful signals that provoke inflammation, which impairs tissue repair and can even cause nearby healthy cells to become senescent. Their presence can lead to many problems: reducing tissue upkeep, increasing chronic inflammation, altering the extracellular matrix, and eventually increasing the risk of cancer and other age-related diseases. Senescent cells and their accumulation are a hallmark of aging.
Cancers, by their nature, create senescent cells, and the relationship between senescent cells and cancer is an intriguing and complex one. While senescence is a protective mechanism against cancer, it can also be a double-edged sword in this respect.
If a cancer becomes firmly established in the tissue and the level of senescent cells is excessive, the senescent cells secrete pro-inflammatory compounds that facilitate the further growth of the cancer rather than preventing it. There is even evidence that cancers such as leukemia may even actively provoke nearby cells to become senescent in order to create this inflammatory environment and thus fuel their expansion.
This review explores the relationship between senescent cells and cancer, specifically bone marrow cancers (hematological malignancies).
Senescence is the irreversible arrest of cell proliferation that has now been shown to play an important role in both health and disease. With increasing age senescent cells accumulate throughout the body, including the bone marrow and this has been associated with a number of age-related pathologies including malignancies. It has been shown that the senescence associated secretory phenotype (SASP) creates a pro-tumoural environment that supports proliferation and survival of malignant cells. Understanding the role of senescent cells in tumor development better may help us to identify new treatment targets to impair tumor survival and reduce treatment resistance. In this review, we will specifically discuss the role of senescence in the aging bone marrow (BM) microenvironment. Many BM disorders are age-related diseases and highly dependent on the BM microenvironment. Despite advances in drug development the prognosis particularly for older patients remains poor and new treatment approaches are needed to improve outcomes for patients. In this review, we will focus on the relationship of senescence and hematological malignancies, how senescence promotes cancer development and how malignant cells induce senescence.
Clearly, there is a close association between cancer and senescence, and prominent researchers of cellular senescence, such as Professor Judith Campisi, were originally from a cancer research background before switching to the study of senescent cells and senolytic drugs that could potentially remove them from the body. We talked with Judith last year about her fascinating research and the link between cancer and senescent cells during an interview at Undoing Aging in Berlin.
Increasing our understanding of the relationship between cancer and senescent cells could lead to better therapies for cancer as well as further our understanding of this aging process. In this context, senolytic drugs capable of destroying senescent cells may be of value for cancer treatment as well as a myriad of other age-related diseases that their presence appears to support.
 Hellmich, C., Moore, J. A., Bowles, K. M., & Rushworth, S. A. (2020). Bone Marrow Senescence and the Microenvironment of Hematological Malignancies. Frontiers in Oncology, 10.