Understanding the biology of colorectal cancer will lead to more rational drug development

Cancer drug development is becoming more targeted and focused as a result of scientific advances.  The understanding of ALK gene rearrangements in lung cancer led to the development of crizotinib (Xalkori) for the subset of patients who are ALK-positive.

Sally Church, Ph.D on Pharma Strategy Blog has reviewed some of the recent advances in our understanding of colororectal cancer (CRC).

Resistance to chemotherapy in colon cancer

The transcription factor AP-2 epsilon (TFAP2E-DKK4) appears to be responsible for some of the resistance to chemotherapy that occurs during colon cancer.

As Sally noted, “the presence of the TFAP2E-DKK4 mutation may explain why some patients with colorectal cancer do better with chemotherapy than others.

Inflammation linked to the early development of colon cancer

Researchers from MD Anderson Cancer Center have identified the role of inflammation and silencing of tumor suppressor genes in early colorectal cancer.

Understanding the biology of the disease could lead to the ability to identify those at high risk of developing colon cancer. Chemopreventative drugs could then be given to this subset of high risk patients to delay the onset of cancer.  An exciting prospect!

Understanding the role of CIMP in early colorectal cancer

CpG island methylator phenotype (CIMP) can occur in 30% of colorectal cancer patients and has been shown to be an independent predictor of survival with 5FU in early or adjuvant CRC.   CIMP may play an important role in tumor development. Expect to hear more on the link between inflammation, DNA methylation and early development of CRC.

Identifying subsets of patients will support rational drug development

Researchers have now shown that BRAF(V600E) mutations occur in 8-10% of colon cancers. The ability to identify this subset of patients could allow therapeutic options to be specifically targeted at them, in the same way that ALK+ lung cancer patients now receive crizotinib.  Previously though, we didn’t know why vemurafenib was showing lack of efficacy in this group. New research has now given us some pointers.

As Sally noted on Pharma Strategy Blog, “a combination of vemurafenib and and an EGFR inhibitor such as as erlotinib, cetuximab or gefitinib, might be a useful clinical approach to try therapeutically in patients with colon cancer harboring the BRAFV600E mutation.”

As we learn more about the biology and early development of colorectal cancer, the ability to undertake rational drug development will increase.  This is good news both for patients and for biotechnology and pharmaceutical companies who want to successfully bring new products to market.

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