To support exciting, perhaps risky, innovative ideas in all areas of basic cancer research. The expectation is that this early-phase grant will enable the researcher to obtain enough preliminary results to apply for competitive external funding.
Breast cancer is the most prevalent and lethal cancer in women. 15% of breast cancers do not overexpress the estrogen, progesterone or HER2 receptors also known as Triple Negative Breast Cancers (TNBC). This type of cancers is more aggressive, has poor prognosis, and lack any targeted therapy. This stems partly from our lack of understanding of driver events in TNBC and for lack of validated targets for its pathogenicity.
Multiple types of circulating tumor cells (CTCs) metastasize into the lung parenchyma by extravasating the pulmonary vasculature. The space between the alveolus and the capillary (approximately 2 um) imposes a significant mechanical barrier on extravasating CTCs that need to squeeze their bulky and stiff nuclei through it with minimal nuclear damage.
The tumor microenvironment affects the survival, development, and progression of cancer. Particularly, it is thought that the transfer of full length mRNA molecules between cancer and normal cells might profoundly affect the local microenvironment. We recently discovered a phenomenon by which full-length mRNAs can be transferred between cells.
Cancer cells tend to acidify their immediate microenvironment due to increased consumption of glucose at limiting oxygen conditions. These unique biophysical properties could be utilized to achieve differential recognition of antigens using the same therapeutic mAbs. Thus, incorporating pH-switchable recognition elements into therapeutic antibodies could result with the desired differential recognition. This would allow increasing the dose of the mAbs to maximize the therapeutic effect while reducing the severity of, or completely eliminate the off-target side effects.
