One prevailing trait often seen in the majority of cancer cells is their impaired ability to undergo normal

differentiation. The occurrence of faulty differentiation is strongly associated with aberrant proliferation, as
explained in Chapter 14. It is well-established that the majority of completely differentiated cells either halt cell
division or engage in few divisions. Instead of undergoing their typical differentiation program, cancer cells
often experience a hinderance in the early stage of differentiation, which aligns with their persistent and
vigorous proliferation.

The leukemias serve as a notable illustration of the correlation between impaired differentiation and the
development of malignancy. The many kinds of blood cells originate from a common progenitor cell located in
the bone marrow (refer to Figure 14.44). Subsequently, the progeny of these cells undergo a commitment
process towards distinct routes of cellular differentiation. Certain cells have the ability to develop into certain
types of blood cells, such as erythrocytes, lymphocytes, granulocytes, or macrophages. The cells of each of
these kinds undergo many rounds of division throughout the process of differentiation. However, once they
reach a completely differentiated state, cell division comes to a halt. In contrast, leukemic cells have a
deficiency in undergoing terminal differentiation (Figure 15.11). However, they are apprehended during the first
phases of their development, during which they maintain their ability to multiply and perpetuate their species.

In Figure 15.11, the illustration depicts the phenomenon of defective differentiation and its association with the
development of leukemia.
In Figure 15.11, the illustration depicts the relationship between defective differentiation and the development
of leukemia. Various categories of blood cells are derived from a multipotential (pluripotent) stem cell located
inside the bone marrow. The precursor cells that give rise to differentiated cells undergo several rounds of cell
division throughout their maturation process. However, the specific details of cell division (more information...)

As elucidated in Chapter 13, programmed cell death, also known as apoptosis, is an essential component of the
differentiating process in several cell types, including blood cells. Numerous cancer cells have a deficiency in
undergoing apoptosis, resulting in prolonged survival rates in comparison to their non-cancerous counterparts.
The inability of cancer cells to undergo apoptosis significantly contributes to the progression of tumors. The
viability of many ordinary cells, for instance, relies on the reception of signals originating from growth factors
or the extracellular matrix, which serve to inhibit apoptosis. On the contrary, tumor cells often exhibit the ability
to endure in the absence of growth substances that are essential for the survival of their normal counterparts. The
inability of tumor cells to undergo apoptosis in the absence of normal environmental cues may have significant
implications not only in the initial formation of tumors but also in the viability and proliferation of metastatic
cells in atypical tissue locations. In response to DNA damage, normal cells often initiate apoptosis, a
programmed cell death mechanism. Conversely, several cancer cells have a deficiency in initiating apoptosis
under similar circumstances. In this particular scenario, the lack of apoptosis plays a role in the development of
resistance among cancer cells against radiation therapy and certain chemotherapeutic agents, which function by
inducing DNA damage. The uncontrolled development of cancer cells in animals is primarily driven by
abnormal cell survival and proliferation.

Please refer to the following topic: "Cell Transformation in Culture."

In order to investigate the process of tumor formation caused by radiation, chemicals, or viruses, it is necessary
to use experimental models that allow for the consistent observation and quantification of the effects induced by
these carcinogenic agents. Assessing the action of carcinogens in intact animals poses challenges in terms of
quantification and control. The advancement of cancer research was significantly propelled by the creation of in
vitro assays that enable the identification of cell transformation, which refers to the conversion of normal cells
to malignant cells in a cultured environment. These tests have been specifically developed to identify
transformed cells, which exhibit the in vitro growth characteristics often seen in tumor cells, subsequent to the
exposure of a culture of normal cells to a carcinogenic substance. The use of their application has allowed the
attainment of a high degree of complexity in the experimental investigation of cell transformation, a feat that
would have been unattainable just via research conducted on complete animals.

The focus test, first devised by Howard Temin and Harry Rubin in 1958, stands as the primary and extensively
used method for assessing cell transformation. The focus test is predicated on the capacity to discern a cluster of
altered cells that exhibit specific morphological characteristics, referred to as a "focus," amongst a backdrop of
normal cells present on the surface of a culture plate (see Figure 15.12). The focus test capitalizes on three
distinct characteristics shown by transformed cells, namely, modified morphology, absence of contact
inhibition, and lack of density-dependent inhibition of growth. The outcome is the development of a colony
comprising of morphologically modified transformed cells that exhibit excessive growth compared to the
surrounding normal cells within the culture. The presence and quantity of these clusters of altered cells can often
be identified and measured within a period of around one to two weeks after exposure to a carcinogenic
substance. In a broad sense, cells that have undergone in vitro transformation have shown the capability to
generate tumors upon introduction into vulnerable organisms, hence substantiating the use of in vitro
transformation as a reliable indication for the development of cancerous cells.