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Tumor Discovery Energy metabolism in bladder cancer

increasing the expression of GLUT1 transporters on their and presence of associated CIS. 6,25,27 Based on a multi-
surface. 11,12 This increased glucose uptake sets the stage institute retrospective study conducted with 2,451 high-
for metabolic competition between effector T cells and grade pT1 patients who were analyzed after treatment
tumor cells. Notably, differentiated CD8 T cells present with BCG, Re-TURBT was beneficial to progression-
+
31
increased reliance on glucose-dependent metabolism in free survival, as well as to overall survival, although only
comparison to their naïve counterparts. Consequently, in cases showing proper muscle absence after the first
38
glucose shortage negatively impacts the effector functions TURBT. Results in the current study are unprecedented;
of CD8 T cells, leading to compromised immune thus, using IBEC in clinical practice presents a potential
+
response and potentially limiting immune checkpoint strategy for aiding therapeutic decision-making, mainly
therapy effectiveness. Furthermore, proapoptotic Bcl-2 for high-grade pTa tumor cases, which are often not
31
23
family members are activated and promote cell apoptosis aggressively treated as pT1 tumors. Cuezva et al. assessed
when glucose uptake is limited. 11,32 Recent studies have IBEC in lung adenocarcinomas and observed that it was
suggested that limited glucose consumption in T cells can lower in large tumors (>3 cm) than in smaller tumors and
be mitigated through inosine or fatty acid metabolism than in lungs without neoplasm. IBEC was also correlated
modulation, although further investigations in this field to tumor stage. IA-stage tumors recorded IBEC 2.5 times
should be conducted. 11,32,33 higher than IB-stage tumors, and it evidenced clear IBEC
correlation to disease prognosis.
As the active players in glycolysis, PFK and GAPDH
play important role in glucose degradation and energy Some high-grade tumors can relapse and progress
generation processes. LDH is another essential protein for to muscle-invasive tumors during follow-up, even
tumor cell metabolism, since it enables pyruvate conversion after aggressive local treatment application (TURBT +
into lactate, which is transported out of the cytoplasm to Re-TURBT + BCG). These patients have worse prognosis
be used by the same cell to produce other molecules or than those with muscle-invasive disease as the initial
39
to be used by the neighboring cells. This process ensures presentation. Moschini et al. retrospectively investigated
tumor cell energy production and substrate supply, even in a group of 768 patients subjected to radical cystectomy
hypoxic and acidic environment, due to high metabolism due to muscle-invasive tumors (475 patients), or due to
and low perfusion. This acidic environment protects the superficial tumors that had progressed to muscle-invasive
tumor cell from apoptosis and enables the invasion of stage, even after intravesical therapies, during follow-up
other tissues. 34,35 LDH indices in the current study were (293 patients). They observed that the non-muscle-
higher in high-grade pT1 tumors than in the other types, invasive group that had progressed during follow-up
likely because it is a more undifferentiated tumor. Thus, recorded worse results for progression/relapse-free
low IBEC in these neoplasms can be an unfavorable factor survival, cancer-specific mortality, and overall mortality
that can be used in therapeutic decision-making, mainly to within 10 years, based on univariate and multivariate
39
indicate another TURBT (Re-TURBT) procedure or even analyses. Therefore, patients with pT1-grade NMIBC
early radical cystectomy. should be subjected to aggressive treatments, such as
early radical cystectomy, mainly in case of BCG failure
There was no change in mitochondrion structure among after TURBT and Re-TURBT. Since high-grade pTa
the investigated groups, neither in immunoreactivity tumors were metabolically similar to pT1, they should
nor in hsp60 protein levels. This finding indicates that be treated in the same way as pT1, especially if they show
mitochondrial function can be restored in high-grade low IBEC. Therefore, IBEC determination can be treated
tumor cases showing decreased oxidative phosphorylation, as an additional tool to help managing these cases,
as previously observed by Fantin et al. 36 particularly under the concerns that treatments applied
High-grade pTa tumors presented metabolic behavior to them are quite aggressive and often lead to significant
quite similar to that of pT1 tumors, high relapse likelihood morbidity.
and progression to muscle-invasive disease; therefore, they
must be subjected to aggressive treatment. High-grade pT1 5. Conclusion
tumors must be subjected to Re-TURBT, from 4 to 6 weeks The aims of the current study were to both feature and
after the first resection, mainly if there is proper muscle compare cell energy metabolism profiles among normal
absence at the first resection, since this change in protocol bladder tissue and NMIBC tissues of different histological
is observed in 10 – 25% of cases. Other prognostic factors grades (such as low-grade pTa, high-grade pTa, and high-
37
that should be taken into consideration in therapeutic grade pT1 tumors). In addition, this study introduced the
decision-making comprise multifocality (>3 lesions), concept of IBEC, which is a new approach applicable to
tumors larger than 3 cm, previous treatment with BCG, treat these tumors. In summary, according to the current

Volume 3 Issue 1 (2024) 12 https://doi.org/10.36922/td.2290