Integrating chemistry, molecular biology and experimental oncology
TARGETING “UNDRUGGABLE” CANCERS
1) Triple-Negative Breast Cancers (TNBCs)
Breast cancers are classified into several molecular subtypes based on a panel of biomarkers, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth receptor factor 1 (HER2) and some others. TNBCs represent approximately 20% of all breast tumour subtypes and are characterized by the lack of ER, PR and HER2 receptors. Therefore, this cancer subtype cannot be treated by hormonal or trastuzumab-based therapy. Current treatment modalities for TNBC are limited and usually involve surgery, radiation therapy or intensive neoadjuvant (before surgery) chemotherapy regimens. However, these treatment modalities demonstrate only limited and short-term success and TNBCs are mainly characterized by a poor prognosis. Despite their aggressive nature, TNBCs have some molecular vulnerabilities, such as increased sensitivity to endoplasmic reticulum stress or metabolic addition to glucose. We are using these molecular vulnerabilities to develop novel effective treatment for this type of breast cancer.
Babak M.V and Ang W.H. et al. Angewandte Chemie Int. Ed., in press, 2021
2) Brain metastases (BMs)
Despite the significant advancements in the treatment of breast cancer, 10–16% of patients develop BM during the late stages of the disease. The unfortunate event of cancer cell spread to the brain from a primary tumor site is associated with poor prognosis and high morbidity. A typical range of survival of breast cancer patients with BMs is only 2–25 months. Treatment options are limited and frequently include surgical resection of the tumor mass and whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS). However, BCBM respond poorly to these treatments, and the therapies serve a mostly palliative function. We are developing novel experimental drug candidates aiming to prevent the formation and growth of brain metastases.
Babak M.V, Zalutsky M. R, Balysnikova I.V. Cancer letters, 489, 174-181, 2020
3) Activation of immune system
Toxic chemotherapy inflicts further distress in patients already suffering from the disease, forcing some of them to opt out of their treatment plans. Prevention of adverse events or more effective management of adverse side/collateral effects arising from anticancer drugs will continue to be an area of urgent need. While chemotherapy aims to eradicate cancer cells, immunotherapy activates the immune system of the patient to ensure clearance of cancer cells and establishment of long-term immunological memory. We aim to develop experimental drugs that will either educate immune cells to recognize and eradicate cancer invaders or activate “immunological visibility” of cancer cells by forced release of “eat me” and “find me” signals.
Tham M.J.R., Babak M.V, Ang W.H. Angewandte Chemie Int. Ed., 59(43), 19070-19078, 2020