Colorectal Cancer Therapeutics: Current and Emerging Treatment Options
Colorectal Cancer Therapeutics: Current and Emerging Treatment Options
Blog Article
Surgery
Surgery is often the first line of treatment for colorectal cancer depending on the stage of cancer. The type of surgery performed will depend on the size and location of the tumor. For early-stage cancers, surgery may be the only treatment needed. Some common surgeries for colorectal cancer include:
Polypectomy - Removes polyps during a colonoscopy before they develop into cancer. Polypectomies can help prevent colorectal cancer.
Lymphadenectomy - Nearby lymph nodes are surgically removed and checked for cancer cells. This helps determine the cancer stage and best treatment approach.
Colectomy - Partial or full removal of the colon depending on the tumor's location. Common procedures include hemicolectomy and total colectomy.
Low Anterior Resection - Removes the lower part of the rectum and reattaches the colon. Often used for mid and low rectal cancers.
Abdominoperineal Resection - Removes the rectum, anus, and surrounding tissue. A colostomy is created for waste diversion. Used for very low rectal cancers.
Chemotherapy
Chemotherapy uses anti-cancer drugs to destroy cancer cells and stop their growth and spread. It is commonly used in Colorectal Cancer Therapeutics as an adjuvant therapy after surgery to reduce the risk of recurrence. Neoadjuvant chemotherapy may also be given before surgery for large tumors to shrink them and make them easier to remove. Some chemotherapy regimens for colorectal cancer include:
5-FU (Fluorouracil) and leucovorin - A classic chemotherapy combination still commonly used today either alone or with other drugs.
FOLFOX - Combines 5-FU, leucovorin, and oxaliplatin. Often used as first-line adjuvant therapy.
FOLFIRI - Pairs 5-FU, leucovorin with irinotecan. Used when cancer recurs or is resistant to FOLFOX.
CAPEOX - Capecitabine is substituted for infused 5-FU along with oxaliplatin. An oral option.
Targeted Therapy
Targeted therapies interfere with specific molecules involved in cancer cell growth and survival. Several targeted drugs have revolutionized colorectal cancer treatment in recent years including:
Bevacizumab (Avastin) - Inhibits vascular endothelial growth factor (VEGF) to block tumor blood supply. Often combined with chemotherapy.
Cetuximab (Erbitux) - Blocks epidermal growth factor receptor (EGFR) signaling in tumors with normal KRAS gene.
Panitumumab (Vectibix) - Another EGFR inhibitor, but only for cancers with wild-type KRAS.
Regorafenib (Stivarga) - Kinase inhibitor for pretreated metastatic colorectal cancer. Blocks tumor growth and angiogenesis.
Aflibercept (Zaltrap) - VEGF trap similar to bevacizumab used with FOLFIRI for late-stage disease.
Radiation Therapy
Radiation therapy utilizes high-energy x-rays or other particles to destroy cancer cells and shrink tumors. It is most commonly used in rectal cancer for:
Neoadjuvant radiation - Given before surgery along with chemotherapy to shrink rectal tumors for easier removal. May avoid permanent colostomy.
Adjuvant radiation - Following surgery to kill any remaining cancer cells and reduce recurrence risk, especially for late-stage or node-positive cancers.
Palliative radiation - To relieve pain and bleeding from advanced metastatic cancers not amenable to other treatments. May provide quality of life benefits.
Immunotherapy
Immunotherapy works to boost the body's own immune response against cancer. Checkpoint inhibitors have shown promise in treating colorectal cancer refractory to other therapies including:
Pembrolizumab (Keytruda) - Anti-PD-1 drug approved for dMMR/MSI-H metastatic colorectal cancer after other treatments fail.
Nivolumab (Opdivo) - Another PD-1 inhibitor investigated for mismatch repair deficient colorectal tumors.
IPI-549 - Inhibits PI3k-γ to activate anti-tumor immunity. Phase 2 trials underway as monotherapy and with chemotherapy.
Future Directions
Promising areas of ongoing research for improved colorectal cancer therapeutics include gut microbiome modulators, viral oncolytic therapies, anti-TGFβ agents, inhibitors of additional immune checkpoints, therapeutic cancer vaccines, and personalized neoadjuvant therapies tailored to individual tumor molecular profiling. As treatment options continue to expand, a multidisciplinary care approach combining the latest surgical, medical, and targeted options provides hope for more colorectal cancer patients.
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