Monitoring the Response to Neoadjuvant Chemotherapy in Breast Cancer

Koga, Kátia Hiromoto; Moriguchi, Sônia Marta; Uemura, J; Pessoa, Eduardo Carvalho; Matthes, Angelo GustavoZucca; Morita, Dilma Mariko

doi:10.5772/53123

Cited by 2 publications

(3 citation statements)

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“…In addition to being inherently resistant to therapies during the course of chemotherapeutic treatments, tumors also acquire resistance towards such therapies. The consequences are 2-fold; first, the tumors acquire resistance with progressive treatment and second, provide impetus to the growth of recurrent tumors (1)(2)(3)(4). CSC subpopulation of the tumor has been held responsible for both therapy resistance and development of tumor recurrences (5-7, 26, 38).…”

Section: Discussionmentioning

confidence: 99%

“…1). Although a majority of LABC patients treated with neoadjuvant chemotherapy (NACT) experience a reduction in tumor size (1), a substantial number either exhibits significant intrinsic resistance or acquire characteristics of multidrug resistance during chemotherapy, i.e., acquired resistance (2,3), thereby limiting the efficacy of chemotherapeutic regimens.…”

Section: Introductionmentioning

confidence: 99%

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Aspirin Suppresses the Acquisition of Chemoresistance in Breast Cancer by Disrupting an NFκB–IL6 Signaling Axis Responsible for the Generation of Cancer Stem Cells

et al. 2016

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Acquired chemoresistance has curtailed cancer survival since the dawn of chemotherapy. Accumulating evidence suggests a major role for cancer stem cells (CSC) in chemoresistance, although their involvement in acquired resistance is still unknown. The use of aspirin has been associated with reduced cancer risk and recurrence, suggesting that the anti-inflammatory drug may exert effects on CSCs. In this study, we investigated the contribution of CSCs to acquired chemoresistance of breast cancer and the avenues for reversing such effects with aspirin. We observed that the residual risk of recurrence was higher in breast cancer patients who had acquired chemoresistance. Treatment of preexisting CSCs with a genotoxic drug combination (5-fluorouracil, doxorubicin, and cyclophosphamide) generated an NFkB-IL6-dependent inflammatory environment that imparted stemness to nonstem cancer cells, induced multidrug resistance, and enhanced the migration potential of CSCs. Treatment with aspirin prior to chemotherapy suppressed the acquisition of chemoresistance by perturbing the nuclear translocation of NFkB in preexisting CSCs. Therefore, disruptions to the NFkB-IL6 feedback loop prevented CSC induction and sensitized preexisting CSCs to chemotherapy. Collectively, our findings suggest that combining aspirin and conventional chemotherapy may offer a new treatment strategy to improve recurrence-free survival of breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aspirin Suppresses the Acquisition of Chemoresistance in Breast Cancer by Disrupting an NFκB–IL6 Signaling Axis Responsible for the Generation of Cancer Stem Cells

et al. 2016

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show abstract

“…The series of experiments outlined in this report focus on doxorubicin because it is one of the key drugs in the standard chemotherapy regimens used for treatment of breast cancer. In fact, around 20%-50% patients with LABC show intrinsic resistance to treatment whereas over 75% of patients acquire resistance with treatment, 59 and the rate of path CR of invasive cancer ranges from 3% to 20% only. 60,61 The existence of therapy-resistant CSCs might be responsible for such a failure of doxorubicin-based conventional therapies.…”

Section: Discussionmentioning

confidence: 99%